Skip to main content
PMC home page
Molecular Pathology : MP logoLink to Molecular Pathology : MP
. 1999 Aug;52(4):179–188. doi: 10.1136/mp.52.4.179

Regulation of E-cadherin: does hypoxia initiate the metastatic cascade?

I R Beavon 1
PMCID: PMC395697  PMID: 10694937

Abstract

The ability of tumours to metastasis is regarded as one of the hallmarks of malignancy. The process through which tumours evolve to achieve this has been termed the metastatic cascade. This cascade has been the subject of much investigation over many years. One of the vital events identified by these investigations is the reduction of adhesion between tumour cells facilitating invasion of the surrounding tissues and vascular channels, ultimately leading to the development of a distant metastasis. E-cadherin and its associated catenin complex have been identified as key molecules in cell adhesion. This review looks at the structure and interaction of the E-cadherin-catenin complex and the factors that appear to regulate E-cadherin expression and thus cell adhesion. From the data gathered, it has become possible to propose the hypothesis that the development of tumour hypoxia is the initiating factor that sets the tumour on the road to metastasis.

Full Text

The Full Text of this article is available as a PDF (210.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aberle H., Bierkamp C., Torchard D., Serova O., Wagner T., Natt E., Wirsching J., Heidkämper C., Montagna M., Lynch H. T. The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6384–6388. doi: 10.1073/pnas.92.14.6384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aberle H., Butz S., Stappert J., Weissig H., Kemler R., Hoschuetzky H. Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J Cell Sci. 1994 Dec;107(Pt 12):3655–3663. doi: 10.1242/jcs.107.12.3655. [DOI] [PubMed] [Google Scholar]
  3. Andrews N. A., Jones A. S., Helliwell T. R., Kinsella A. R. Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. Br J Cancer. 1997;75(10):1474–1480. doi: 10.1038/bjc.1997.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Balda M. S., Gonzalez-Mariscal L., Matter K., Cereijido M., Anderson J. M. Assembly of the tight junction: the role of diacylglycerol. J Cell Biol. 1993 Oct;123(2):293–302. doi: 10.1083/jcb.123.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Banks R. E., Porter W. H., Whelan P., Smith P. H., Selby P. J. Soluble forms of the adhesion molecule E-cadherin in urine. J Clin Pathol. 1995 Feb;48(2):179–180. doi: 10.1136/jcp.48.2.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baserga R. Oncogenes and the strategy of growth factors. Cell. 1994 Dec 16;79(6):927–930. doi: 10.1016/0092-8674(94)90023-x. [DOI] [PubMed] [Google Scholar]
  7. Becker J. W., Erickson H. P., Hoffman S., Cunningham B. A., Edelman G. M. Topology of cell adhesion molecules. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1088–1092. doi: 10.1073/pnas.86.3.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Becker K. F., Atkinson M. J., Reich U., Huang H. H., Nekarda H., Siewert J. R., Höfler H. Exon skipping in the E-cadherin gene transcript in metastatic human gastric carcinomas. Hum Mol Genet. 1993 Jun;2(6):803–804. doi: 10.1093/hmg/2.6.803. [DOI] [PubMed] [Google Scholar]
  9. Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
  10. Bernstein L. R., Liotta L. A. Molecular mediators of interactions with extracellular matrix components in metastasis and angiogenesis. Curr Opin Oncol. 1994 Jan;6(1):106–113. doi: 10.1097/00001622-199401000-00015. [DOI] [PubMed] [Google Scholar]
  11. Berx G., Staes K., van Hengel J., Molemans F., Bussemakers M. J., van Bokhoven A., van Roy F. Cloning and characterization of the human invasion suppressor gene E-cadherin (CDH1). Genomics. 1995 Mar 20;26(2):281–289. doi: 10.1016/0888-7543(95)80212-5. [DOI] [PubMed] [Google Scholar]
  12. Birchmeier C., Birchmeier W. Molecular aspects of mesenchymal-epithelial interactions. Annu Rev Cell Biol. 1993;9:511–540. doi: 10.1146/annurev.cb.09.110193.002455. [DOI] [PubMed] [Google Scholar]
  13. Birchmeier W., Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994 May 27;1198(1):11–26. doi: 10.1016/0304-419x(94)90003-5. [DOI] [PubMed] [Google Scholar]
  14. Bockmühl U., Petersen S., Schmidt S., Wolf G., Jahnke V., Dietel M., Petersen I. Patterns of chromosomal alterations in metastasizing and nonmetastasizing primary head and neck carcinomas. Cancer Res. 1997 Dec 1;57(23):5213–5216. [PubMed] [Google Scholar]
  15. Bodmer W., Bishop T., Karran P. Genetic steps in colorectal cancer. Nat Genet. 1994 Mar;6(3):217–219. doi: 10.1038/ng0394-217. [DOI] [PubMed] [Google Scholar]
  16. Bongiorno P. F., al-Kasspooles M., Lee S. W., Rachwal W. J., Moore J. H., Whyte R. I., Orringer M. B., Beer D. G. E-cadherin expression in primary and metastatic thoracic neoplasms and in Barrett's oesophagus. Br J Cancer. 1995 Jan;71(1):166–172. doi: 10.1038/bjc.1995.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Boros P., Miller C. M. Hepatocyte growth factor: a multifunctional cytokine. Lancet. 1995 Feb 4;345(8945):293–295. doi: 10.1016/s0140-6736(95)90279-1. [DOI] [PubMed] [Google Scholar]
  18. Brabant G., Hoang-Vu C., Cetin Y., Dralle H., Scheumann G., Mölne J., Hansson G., Jansson S., Ericson L. E., Nilsson M. E-cadherin: a differentiation marker in thyroid malignancies. Cancer Res. 1993 Oct 15;53(20):4987–4993. [PubMed] [Google Scholar]
  19. Breen E., Clarke A., Steele G., Jr, Mercurio A. M. Poorly differentiated colon carcinoma cell lines deficient in alpha-catenin expression express high levels of surface E-cadherin but lack Ca(2+)-dependent cell-cell adhesion. Cell Adhes Commun. 1993 Dec;1(3):239–250. doi: 10.3109/15419069309097257. [DOI] [PubMed] [Google Scholar]
  20. Bringuier P. P., Umbas R., Schaafsma H. E., Karthaus H. F., Debruyne F. M., Schalken J. A. Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 1993 Jul 15;53(14):3241–3245. [PubMed] [Google Scholar]
  21. Brizel D. M., Scully S. P., Harrelson J. M., Layfield L. J., Bean J. M., Prosnitz L. R., Dewhirst M. W. Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res. 1996 Mar 1;56(5):941–943. [PubMed] [Google Scholar]
  22. Brizel D. M., Sibley G. S., Prosnitz L. R., Scher R. L., Dewhirst M. W. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):285–289. doi: 10.1016/s0360-3016(97)00101-6. [DOI] [PubMed] [Google Scholar]
  23. Buckley C. D., Simmons D. L. Cell adhesion: a new target for therapy. Mol Med Today. 1997 Oct;3(10):449–456. doi: 10.1016/S1357-4310(97)01128-3. [DOI] [PubMed] [Google Scholar]
  24. Bussemakers M. J., Schalken J. A. The role of cell adhesion molecules and proteases in tumor invasion and metastasis. World J Urol. 1996;14(3):151–156. doi: 10.1007/BF00186894. [DOI] [PubMed] [Google Scholar]
  25. Butz S., Kemler R. Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell adhesion. FEBS Lett. 1994 Nov 28;355(2):195–200. doi: 10.1016/0014-5793(94)01205-9. [DOI] [PubMed] [Google Scholar]
  26. Böhm M., Totzeck B., Birchmeier W., Wieland I. Differences of E-cadherin expression levels and patterns in primary and metastatic human lung cancer. Clin Exp Metastasis. 1994 Jan;12(1):55–62. doi: 10.1007/BF01784334. [DOI] [PubMed] [Google Scholar]
  27. Carey T. E., Frank C. J., Raval J. R., Jones J. W., McClatchey K. D., Beals T. F., Worsham M. J., Van Dyke D. L. Identifying genetic changes associated with tumor progression in squamous cell carcinoma. Acta Otolaryngol Suppl. 1997;529:229–232. doi: 10.3109/00016489709124130. [DOI] [PubMed] [Google Scholar]
  28. Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol. 1995;19 (Suppl 1):S37–S43. [PubMed] [Google Scholar]
  29. Coutifaris C., Kao L. C., Sehdev H. M., Chin U., Babalola G. O., Blaschuk O. W., Strauss J. F., 3rd E-cadherin expression during the differentiation of human trophoblasts. Development. 1991 Nov;113(3):767–777. doi: 10.1242/dev.113.3.767. [DOI] [PubMed] [Google Scholar]
  30. Cover T. L., Blaser M. J. Helicobacter pylori and gastroduodenal disease. Annu Rev Med. 1992;43:135–145. doi: 10.1146/annurev.me.43.020192.001031. [DOI] [PubMed] [Google Scholar]
  31. Cowley G. P., Smith M. E. Modulation of E-cadherin expression and morphological phenotype in the intravascular component of adenocarcinomas. Int J Cancer. 1995 Jan 27;60(3):325–329. doi: 10.1002/ijc.2910600308. [DOI] [PubMed] [Google Scholar]
  32. Crossin K. L., Chuong C. M., Edelman G. M. Expression sequences of cell adhesion molecules. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6942–6946. doi: 10.1073/pnas.82.20.6942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Cuvier C., Jang A., Hill R. P. Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity of murine tumor cells and correlation with cathepsin (L + B) secretion. Clin Exp Metastasis. 1997 Jan;15(1):19–25. doi: 10.1023/a:1018428105463. [DOI] [PubMed] [Google Scholar]
  34. Damsky C. H., Werb Z. Signal transduction by integrin receptors for extracellular matrix: cooperative processing of extracellular information. Curr Opin Cell Biol. 1992 Oct;4(5):772–781. doi: 10.1016/0955-0674(92)90100-q. [DOI] [PubMed] [Google Scholar]
  35. Daniel J. M., Reynolds A. B. The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. Mol Cell Biol. 1995 Sep;15(9):4819–4824. doi: 10.1128/mcb.15.9.4819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. De Benedetti L., Sciallero S., Gismondi V., James R., Bafico A., Biticchi R., Masetti E., Bonelli L., Heouaine A., Picasso M. Association of APC gene mutations and histological characteristics of colorectal adenomas. Cancer Res. 1994 Jul 1;54(13):3553–3556. [PubMed] [Google Scholar]
  37. De Leeuw W. J., Berx G., Vos C. B., Peterse J. L., Van de Vijver M. J., Litvinov S., Van Roy F., Cornelisse C. J., Cleton-Jansen A. M. Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997 Dec;183(4):404–411. doi: 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  38. Dorkin T. J., Robson C. N., Neal D. E. The molecular pathology of urological malignancies. J Pathol. 1997 Dec;183(4):380–387. doi: 10.1002/(SICI)1096-9896(199712)183:4<380::AID-PATH959>3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
  39. Dorudi S., Sheffield J. P., Poulsom R., Northover J. M., Hart I. R. E-cadherin expression in colorectal cancer. An immunocytochemical and in situ hybridization study. Am J Pathol. 1993 Apr;142(4):981–986. [PMC free article] [PubMed] [Google Scholar]
  40. Doğan A., Wang Z. D., Spencer J. E-cadherin expression in intestinal epithelium. J Clin Pathol. 1995 Feb;48(2):143–146. doi: 10.1136/jcp.48.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ellis V., Pyke C., Eriksen J., Solberg H., Danø K. The urokinase receptor: involvement in cell surface proteolysis and cancer invasion. Ann N Y Acad Sci. 1992 Dec 4;667:13–31. doi: 10.1111/j.1749-6632.1992.tb51591.x. [DOI] [PubMed] [Google Scholar]
  42. Falanga V., Takagi H., Ceballos P. I., Pardes J. B. Low oxygen tension decreases receptor binding of peptide growth factors in dermal fibroblast cultures. Exp Cell Res. 1994 Jul;213(1):80–84. doi: 10.1006/excr.1994.1175. [DOI] [PubMed] [Google Scholar]
  43. Fidler I. J., Hart I. R. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982 Sep 10;217(4564):998–1003. doi: 10.1126/science.7112116. [DOI] [PubMed] [Google Scholar]
  44. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  45. Frixen U. H., Nagamine Y. Stimulation of urokinase-type plasminogen activator expression by blockage of E-cadherin-dependent cell-cell adhesion. Cancer Res. 1993 Aug 1;53(15):3618–3623. [PubMed] [Google Scholar]
  46. Gamallo C., Palacios J., Suarez A., Pizarro A., Navarro P., Quintanilla M., Cano A. Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol. 1993 Apr;142(4):987–993. [PMC free article] [PubMed] [Google Scholar]
  47. Glück U., Rodríguez Fernández J. L., Pankov R., Ben-Ze'ev A. Regulation of adherens junction protein expression in growth-activated 3T3 cells and in regenerating liver. Exp Cell Res. 1992 Oct;202(2):477–486. doi: 10.1016/0014-4827(92)90102-e. [DOI] [PubMed] [Google Scholar]
  48. Gupta S. K., Douglas-Jones A. G., Jasani B., Morgan J. M., Pignatelli M., Mansel R. E. E-cadherin (E-cad) expression in duct carcinoma in situ (DCIS) of the breast. Virchows Arch. 1997 Jan;430(1):23–28. doi: 10.1007/BF01008012. [DOI] [PubMed] [Google Scholar]
  49. Hart I. R., Saini A. Biology of tumour metastasis. Lancet. 1992 Jun 13;339(8807):1453–1457. doi: 10.1016/0140-6736(92)92039-i. [DOI] [PubMed] [Google Scholar]
  50. Herrenknecht K., Ozawa M., Eckerskorn C., Lottspeich F., Lenter M., Kemler R. The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9156–9160. doi: 10.1073/pnas.88.20.9156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Hill R. P. Tumor progression: potential role of unstable genomic changes. Cancer Metastasis Rev. 1990 Sep;9(2):137–147. doi: 10.1007/BF00046340. [DOI] [PubMed] [Google Scholar]
  52. Hinck L., Nelson W. J., Papkoff J. Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin. J Cell Biol. 1994 Mar;124(5):729–741. doi: 10.1083/jcb.124.5.729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Hinck L., Näthke I. S., Papkoff J., Nelson W. J. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994 Jun;125(6):1327–1340. doi: 10.1083/jcb.125.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Hirose T., Terajima H., Yamauchi A., Kinoshita K., Furuke K., Gomi T., Kawai Y., Tsuyuki S., Nakamura Y., Ikai I. Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes. J Hepatol. 1997 Dec;27(6):1081–1088. doi: 10.1016/s0168-8278(97)80152-3. [DOI] [PubMed] [Google Scholar]
  55. Homma T., Sakai M., Cheng H. F., Yasuda T., Coffey R. J., Jr, Harris R. C. Induction of heparin-binding epidermal growth factor-like growth factor mRNA in rat kidney after acute injury. J Clin Invest. 1995 Aug;96(2):1018–1025. doi: 10.1172/JCI118087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Hoschuetzky H., Aberle H., Kemler R. Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 1994 Dec;127(5):1375–1380. doi: 10.1083/jcb.127.5.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Hunt N. C., Douglas-Jones A. G., Jasani B., Morgan J. M., Pignatelli M. Loss of E-cadherin expression associated with lymph node metastases in small breast carcinomas. Virchows Arch. 1997 Apr;430(4):285–289. doi: 10.1007/BF01092751. [DOI] [PubMed] [Google Scholar]
  58. Hunter T. Oncoprotein networks. Cell. 1997 Feb 7;88(3):333–346. doi: 10.1016/s0092-8674(00)81872-3. [DOI] [PubMed] [Google Scholar]
  59. Hülsken J., Birchmeier W., Behrens J. E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. J Cell Biol. 1994 Dec;127(6 Pt 2):2061–2069. doi: 10.1083/jcb.127.6.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Inoue M., Ogawa H., Miyata M., Shiozaki H., Tanizawa O. Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs. Am J Clin Pathol. 1992 Jul;98(1):76–80. doi: 10.1093/ajcp/98.1.76. [DOI] [PubMed] [Google Scholar]
  61. Isaacson P. G. Recent developments in our understanding of gastric lymphomas. Am J Surg Pathol. 1996;20 (Suppl 1):S1–S7. doi: 10.1097/00000478-199600001-00002. [DOI] [PubMed] [Google Scholar]
  62. Jang A., Hill R. P. An examination of the effects of hypoxia, acidosis, and glucose starvation on the expression of metastasis-associated genes in murine tumor cells. Clin Exp Metastasis. 1997 Sep;15(5):469–483. doi: 10.1023/a:1018470709523. [DOI] [PubMed] [Google Scholar]
  63. Jiang W. G. E-cadherin and its associated protein catenins, cancer invasion and metastasis. Br J Surg. 1996 Apr;83(4):437–446. doi: 10.1002/bjs.1800830404. [DOI] [PubMed] [Google Scholar]
  64. Jones J. L., Royall J. E., Walker R. A. E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma. Br J Cancer. 1996 Oct;74(8):1237–1241. doi: 10.1038/bjc.1996.522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Jou T. S., Stewart D. B., Stappert J., Nelson W. J., Marrs J. A. Genetic and biochemical dissection of protein linkages in the cadherin-catenin complex. Proc Natl Acad Sci U S A. 1995 May 23;92(11):5067–5071. doi: 10.1073/pnas.92.11.5067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Juliano R. L., Varner J. A. Adhesion molecules in cancer: the role of integrins. Curr Opin Cell Biol. 1993 Oct;5(5):812–818. doi: 10.1016/0955-0674(93)90030-t. [DOI] [PubMed] [Google Scholar]
  67. Kadowaki T., Shiozaki H., Inoue M., Tamura S., Oka H., Doki Y., Iihara K., Matsui S., Iwazawa T., Nagafuchi A. E-cadherin and alpha-catenin expression in human esophageal cancer. Cancer Res. 1994 Jan 1;54(1):291–296. [PubMed] [Google Scholar]
  68. Kanai Y., Oda T., Tsuda H., Ochiai A., Hirohashi S. Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast. Jpn J Cancer Res. 1994 Oct;85(10):1035–1039. doi: 10.1111/j.1349-7006.1994.tb02902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Katayama M., Hirai S., Kamihagi K., Nakagawa K., Yasumoto M., Kato I. Soluble E-cadherin fragments increased in circulation of cancer patients. Br J Cancer. 1994 Mar;69(3):580–585. doi: 10.1038/bjc.1994.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Kawanishi J., Kato J., Sasaki K., Fujii S., Watanabe N., Niitsu Y. Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39. Mol Cell Biol. 1995 Mar;15(3):1175–1181. doi: 10.1128/mcb.15.3.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Knudsen K. A., Wheelock M. J. Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin. J Cell Biol. 1992 Aug;118(3):671–679. doi: 10.1083/jcb.118.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Kraus C., Liehr T., Hülsken J., Behrens J., Birchmeier W., Grzeschik K. H., Ballhausen W. G. Localization of the human beta-catenin gene (CTNNB1) to 3p21: a region implicated in tumor development. Genomics. 1994 Sep 1;23(1):272–274. doi: 10.1006/geno.1994.1493. [DOI] [PubMed] [Google Scholar]
  73. Kuroda S., Fukata M., Nakagawa M., Fujii K., Nakamura T., Ookubo T., Izawa I., Nagase T., Nomura N., Tani H. Role of IQGAP1, a target of the small GTPases Cdc42 and Rac1, in regulation of E-cadherin- mediated cell-cell adhesion. Science. 1998 Aug 7;281(5378):832–835. doi: 10.1126/science.281.5378.832. [DOI] [PubMed] [Google Scholar]
  74. Le Bivic A., Sambuy Y., Mostov K., Rodriguez-Boulan E. Vectorial targeting of an endogenous apical membrane sialoglycoprotein and uvomorulin in MDCK cells. J Cell Biol. 1990 May;110(5):1533–1539. doi: 10.1083/jcb.110.5.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Liotta L. A., Steeg P. S., Stetler-Stevenson W. G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991 Jan 25;64(2):327–336. doi: 10.1016/0092-8674(91)90642-c. [DOI] [PubMed] [Google Scholar]
  76. Löffler M. Restimulation of cell cycle progression by hypoxic tumour cells with deoxynucleosides requires ppm oxygen tension. Exp Cell Res. 1987 Mar;169(1):255–261. doi: 10.1016/0014-4827(87)90243-6. [DOI] [PubMed] [Google Scholar]
  77. Maiese K., Boniece I., DeMeo D., Wagner J. A. Peptide growth factors protect against ischemia in culture by preventing nitric oxide toxicity. J Neurosci. 1993 Jul;13(7):3034–3040. doi: 10.1523/JNEUROSCI.13-07-03034.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Mansouri A., Spurr N., Goodfellow P. N., Kemler R. Characterization and chromosomal localization of the gene encoding the human cell adhesion molecule uvomorulin. Differentiation. 1988 Jun;38(1):67–71. doi: 10.1111/j.1432-0436.1988.tb00593.x. [DOI] [PubMed] [Google Scholar]
  79. Mareel M., Bracke M., Van Roy F. Invasion promoter versus invasion suppressor molecules: the paradigm of E-cadherin. Mol Biol Rep. 1994 Jan;19(1):45–67. doi: 10.1007/BF00987321. [DOI] [PubMed] [Google Scholar]
  80. Matrisian L. M. The matrix-degrading metalloproteinases. Bioessays. 1992 Jul;14(7):455–463. doi: 10.1002/bies.950140705. [DOI] [PubMed] [Google Scholar]
  81. Mattijssen V., Peters H. M., Schalkwijk L., Manni J. J., van 't Hof-Grootenboer B., de Mulder P. H., Ruiter D. J. E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. Int J Cancer. 1993 Oct 21;55(4):580–585. doi: 10.1002/ijc.2910550411. [DOI] [PubMed] [Google Scholar]
  82. Mayer B., Johnson J. P., Leitl F., Jauch K. W., Heiss M. M., Schildberg F. W., Birchmeier W., Funke I. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993 Apr 1;53(7):1690–1695. [PubMed] [Google Scholar]
  83. McCrea P. D., Gumbiner B. M. Purification of a 92-kDa cytoplasmic protein tightly associated with the cell-cell adhesion molecule E-cadherin (uvomorulin). Characterization and extractability of the protein complex from the cell cytostructure. J Biol Chem. 1991 Mar 5;266(7):4514–4520. [PubMed] [Google Scholar]
  84. McPherson J. D., Morton R. A., Ewing C. M., Wasmuth J. J., Overhauser J., Nagafuchi A., Tsukita S., Isaacs W. B. Assignment of the human alpha-catenin gene (CTNNA1) to chromosome 5q21-q22. Genomics. 1994 Jan 1;19(1):188–190. doi: 10.1006/geno.1994.1042. [DOI] [PubMed] [Google Scholar]
  85. Miyaki M., Konishi M., Kikuchi-Yanoshita R., Enomoto M., Igari T., Tanaka K., Muraoka M., Takahashi H., Amada Y., Fukayama M. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res. 1994 Jun 1;54(11):3011–3020. [PubMed] [Google Scholar]
  86. Moll R., Mitze M., Frixen U. H., Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol. 1993 Dec;143(6):1731–1742. [PMC free article] [PubMed] [Google Scholar]
  87. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  88. Moon R. T., Brown J. D., Torres M. WNTs modulate cell fate and behavior during vertebrate development. Trends Genet. 1997 Apr;13(4):157–162. doi: 10.1016/s0168-9525(97)01093-7. [DOI] [PubMed] [Google Scholar]
  89. Morton R. A., Ewing C. M., Nagafuchi A., Tsukita S., Isaacs W. B. Reduction of E-cadherin levels and deletion of the alpha-catenin gene in human prostate cancer cells. Cancer Res. 1993 Aug 1;53(15):3585–3590. [PubMed] [Google Scholar]
  90. Nabi I. R., Watanabe H., Raz A. Autocrine motility factor and its receptor: role in cell locomotion and metastasis. Cancer Metastasis Rev. 1992 Mar;11(1):5–20. doi: 10.1007/BF00047599. [DOI] [PubMed] [Google Scholar]
  91. Nagafuchi A., Takeichi M. Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. Cell Regul. 1989 Nov;1(1):37–44. doi: 10.1091/mbc.1.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Nathanson S. D., Westrick P., Anaya P., Hetzel F. W., Jacobsen G. Relationship of spontaneous regional lymph node metastases to dose of local irradiation of primary B16 melanomas. Cancer Res. 1989 Aug 15;49(16):4412–4416. [PubMed] [Google Scholar]
  93. Navarro P., Lozano E., Cano A. Expression of E- or P-cadherin is not sufficient to modify the morphology and the tumorigenic behavior of murine spindle carcinoma cells. Possible involvement of plakoglobin. J Cell Sci. 1993 Aug;105(Pt 4):923–934. doi: 10.1242/jcs.105.4.923. [DOI] [PubMed] [Google Scholar]
  94. Nicholson L. J., Pei X. F., Watt F. M. Expression of E-cadherin, P-cadherin and involucrin by normal and neoplastic keratinocytes in culture. Carcinogenesis. 1991 Jul;12(7):1345–1349. doi: 10.1093/carcin/12.7.1345. [DOI] [PubMed] [Google Scholar]
  95. Nicolson G. L. Generation of phenotypic diversity and progression in metastatic tumor cells. Cancer Metastasis Rev. 1984;3(1):25–42. doi: 10.1007/BF00047691. [DOI] [PubMed] [Google Scholar]
  96. Nicolson G. L. Molecular mechanisms of cancer metastasis: tumor and host properties and the role of oncogenes and suppressor genes. Curr Opin Oncol. 1991 Feb;3(1):75–92. [PubMed] [Google Scholar]
  97. Näthke I. S., Hinck L., Swedlow J. R., Papkoff J., Nelson W. J. Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells. J Cell Biol. 1994 Jun;125(6):1341–1352. doi: 10.1083/jcb.125.6.1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Oda T., Kanai Y., Shimoyama Y., Nagafuchi A., Tsukita S., Hirohashi S. Cloning of the human alpha-catenin cDNA and its aberrant mRNA in a human cancer cell line. Biochem Biophys Res Commun. 1993 Jun 30;193(3):897–904. doi: 10.1006/bbrc.1993.1710. [DOI] [PubMed] [Google Scholar]
  99. Oka H., Shiozaki H., Kobayashi K., Inoue M., Tahara H., Kobayashi T., Takatsuka Y., Matsuyoshi N., Hirano S., Takeichi M. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993 Apr 1;53(7):1696–1701. [PubMed] [Google Scholar]
  100. Otto T., Birchmeier W., Schmidt U., Hinke A., Schipper J., Rübben H., Raz A. Inverse relation of E-cadherin and autocrine motility factor receptor expression as a prognostic factor in patients with bladder carcinomas. Cancer Res. 1994 Jun 15;54(12):3120–3123. [PubMed] [Google Scholar]
  101. Otto T., Rembrink K., Goepel M., Meyer-Schwickerath M., Rübben H. E-cadherin: a marker for differentiation and invasiveness in prostatic carcinoma. Urol Res. 1993;21(5):359–362. doi: 10.1007/BF00296837. [DOI] [PubMed] [Google Scholar]
  102. Overduin M., Harvey T. S., Bagby S., Tong K. I., Yau P., Takeichi M., Ikura M. Solution structure of the epithelial cadherin domain responsible for selective cell adhesion. Science. 1995 Jan 20;267(5196):386–389. doi: 10.1126/science.7824937. [DOI] [PubMed] [Google Scholar]
  103. Oyama T., Kanai Y., Ochiai A., Akimoto S., Oda T., Yanagihara K., Nagafuchi A., Tsukita S., Shibamoto S., Ito F. A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res. 1994 Dec 1;54(23):6282–6287. [PubMed] [Google Scholar]
  104. Ozawa M., Baribault H., Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. doi: 10.1002/j.1460-2075.1989.tb03563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Ozawa M., Kemler R. Correct proteolytic cleavage is required for the cell adhesive function of uvomorulin. J Cell Biol. 1990 Oct;111(4):1645–1650. doi: 10.1083/jcb.111.4.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Ozawa M., Ringwald M., Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4246–4250. doi: 10.1073/pnas.87.11.4246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Palacios J., Benito N., Pizarro A., Suárez A., Espada J., Cano A., Gamallo C. Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features. Am J Pathol. 1995 Mar;146(3):605–612. [PMC free article] [PubMed] [Google Scholar]
  108. Panico L., D'Antonio A., Salvatore G., Mezza E., Tortora G., De Laurentiis M., De Placido S., Giordano T., Merino M., Salomon D. S. Differential immunohistochemical detection of transforming growth factor alpha, amphiregulin and CRIPTO in human normal and malignant breast tissues. Int J Cancer. 1996 Jan 3;65(1):51–56. doi: 10.1002/(SICI)1097-0215(19960103)65:1<51::AID-IJC9>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  109. Pignatelli M., Ansari T. W., Gunter P., Liu D., Hirano S., Takeichi M., Klöppel G., Lemoine N. R. Loss of membranous E-cadherin expression in pancreatic cancer: correlation with lymph node metastasis, high grade, and advanced stage. J Pathol. 1994 Dec;174(4):243–248. doi: 10.1002/path.1711740403. [DOI] [PubMed] [Google Scholar]
  110. Pilichowska M., Kimura N., Fujiwara H., Nagura H. Immunohistochemical study of TGF-alpha, TGF-beta1, EGFR, and IGF-1 expression in human breast carcinoma. Mod Pathol. 1997 Oct;10(10):969–975. [PubMed] [Google Scholar]
  111. Pizarro A., Benito N., Navarro P., Palacios J., Cano A., Quintanilla M., Contreras F., Gamallo C. E-cadherin expression in basal cell carcinoma. Br J Cancer. 1994 Jan;69(1):157–162. doi: 10.1038/bjc.1994.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Powell S. M., Zilz N., Beazer-Barclay Y., Bryan T. M., Hamilton S. R., Thibodeau S. N., Vogelstein B., Kinzler K. W. APC mutations occur early during colorectal tumorigenesis. Nature. 1992 Sep 17;359(6392):235–237. doi: 10.1038/359235a0. [DOI] [PubMed] [Google Scholar]
  113. Ramsay J., Suit H. D., Sedlacek R. Experimental studies on the incidence of metastases after failure of radiation treatment and the effect of salvage surgery. Int J Radiat Oncol Biol Phys. 1988 Jun;14(6):1165–1168. doi: 10.1016/0360-3016(88)90394-x. [DOI] [PubMed] [Google Scholar]
  114. Rasbridge S. A., Gillett C. E., Sampson S. A., Walsh F. S., Millis R. R. Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma. J Pathol. 1993 Feb;169(2):245–250. doi: 10.1002/path.1711690211. [DOI] [PubMed] [Google Scholar]
  115. Reima I., Lehtonen E., Virtanen I., Fléchon J. E. The cytoskeleton and associated proteins during cleavage, compaction and blastocyst differentiation in the pig. Differentiation. 1993 Aug;54(1):35–45. doi: 10.1111/j.1432-0436.1993.tb00657.x. [DOI] [PubMed] [Google Scholar]
  116. Rennie J. Mutable mutation. Some genes cause diseases by growing and growing and... Sci Am. 1992 May;266(5):34–34. [PubMed] [Google Scholar]
  117. Reynolds A. B., Daniel J., McCrea P. D., Wheelock M. J., Wu J., Zhang Z. Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. Mol Cell Biol. 1994 Dec;14(12):8333–8342. doi: 10.1128/mcb.14.12.8333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Reynolds A. B., Jenkins N. A., Gilbert D. J., Copeland N. G., Shapiro D. N., Wu J., Daniel J. M. The gene encoding p120cas, a novel catenin, localizes on human chromosome 11q11 (CTNND) and mouse chromosome 2 (Catns). Genomics. 1996 Jan 1;31(1):127–129. doi: 10.1006/geno.1996.0020. [DOI] [PubMed] [Google Scholar]
  119. Rice G. C., Hoy C., Schimke R. T. Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5978–5982. doi: 10.1073/pnas.83.16.5978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Rice G. C., Ling V., Schimke R. T. Frequencies of independent and simultaneous selection of Chinese hamster cells for methotrexate and doxorubicin (adriamycin) resistance. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9261–9264. doi: 10.1073/pnas.84.24.9261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Risinger J. I., Berchuck A., Kohler M. F., Boyd J. Mutations of the E-cadherin gene in human gynecologic cancers. Nat Genet. 1994 May;7(1):98–102. doi: 10.1038/ng0594-98. [DOI] [PubMed] [Google Scholar]
  122. Rosen E. M., Nigam S. K., Goldberg I. D. Scatter factor and the c-met receptor: a paradigm for mesenchymal/epithelial interaction. J Cell Biol. 1994 Dec;127(6 Pt 2):1783–1787. doi: 10.1083/jcb.127.6.1783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Rubinfeld B., Souza B., Albert I., Müller O., Chamberlain S. H., Masiarz F. R., Munemitsu S., Polakis P. Association of the APC gene product with beta-catenin. Science. 1993 Dec 10;262(5140):1731–1734. doi: 10.1126/science.8259518. [DOI] [PubMed] [Google Scholar]
  124. Ruiz P., Günthert U. The cellular basis of metastasis. World J Urol. 1996;14(3):141–150. doi: 10.1007/BF00186893. [DOI] [PubMed] [Google Scholar]
  125. Sakai M., Zhang M., Homma T., Garrick B., Abraham J. A., McKanna J. A., Harris R. C. Production of heparin binding epidermal growth factor-like growth factor in the early phase of regeneration after acute renal injury. Isolation and localization of bioactive molecules. J Clin Invest. 1997 May 1;99(9):2128–2138. doi: 10.1172/JCI119386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Sakaki T., Wato M., Kaji R., Mushimoto K., Shirasu R., Tanaka A. Correlation of E- and P-cadherin expression with differentiation grade and mode of invasion in gingival carcinoma. Pathol Int. 1994 Apr;44(4):280–286. doi: 10.1111/j.1440-1827.1994.tb03365.x. [DOI] [PubMed] [Google Scholar]
  127. Sakuragi N., Nishiya M., Ikeda K., Ohkouch T., Furth E. E., Hareyama H., Satoh C., Fujimoto S. Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol. 1994 May;53(2):183–189. doi: 10.1006/gyno.1994.1113. [DOI] [PubMed] [Google Scholar]
  128. Scherer G., Bausch E., Gaa A., von Deimling O. Gene mapping on mouse chromosome 8 by interspecific crosses: new data on a linkage group conserved on human chromosome 16q. Genomics. 1989 Aug;5(2):275–282. doi: 10.1016/0888-7543(89)90058-x. [DOI] [PubMed] [Google Scholar]
  129. Shapiro L., Fannon A. M., Kwong P. D., Thompson A., Lehmann M. S., Grübel G., Legrand J. F., Als-Nielsen J., Colman D. R., Hendrickson W. A. Structural basis of cell-cell adhesion by cadherins. Nature. 1995 Mar 23;374(6520):327–337. doi: 10.1038/374327a0. [DOI] [PubMed] [Google Scholar]
  130. Shibamoto S., Hayakawa M., Takeuchi K., Hori T., Miyazawa K., Kitamura N., Johnson K. R., Wheelock M. J., Matsuyoshi N., Takeichi M. Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. J Cell Biol. 1995 Mar;128(5):949–957. doi: 10.1083/jcb.128.5.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  131. Shimoyama Y., Nagafuchi A., Fujita S., Gotoh M., Takeichi M., Tsukita S., Hirohashi S. Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell-cell adhesiveness. Cancer Res. 1992 Oct 15;52(20):5770–5774. [PubMed] [Google Scholar]
  132. Shino Y., Watanabe A., Yamada Y., Tanase M., Yamada T., Matsuda M., Yamashita J., Tatsumi M., Miwa T., Nakano H. Clinicopathologic evaluation of immunohistochemical E-cadherin expression in human gastric carcinomas. Cancer. 1995 Dec 1;76(11):2193–2201. doi: 10.1002/1097-0142(19951201)76:11<2193::aid-cncr2820761104>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  133. Shiozaki H., Kadowaki T., Doki Y., Inoue M., Tamura S., Oka H., Iwazawa T., Matsui S., Shimaya K., Takeichi M. Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line. Br J Cancer. 1995 Feb;71(2):250–258. doi: 10.1038/bjc.1995.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  134. Shiozaki H., Oka H., Inoue M., Tamura S., Monden M. E-cadherin mediated adhesion system in cancer cells. Cancer. 1996 Apr 15;77(8 Suppl):1605–1613. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1605::AID-CNCR28>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  135. Shrieve D. C., Begg A. C. Cell cycle kinetics of aerated, hypoxic and re-aerated cells in vitro using flow cytometric determination of cellular DNA and incorporated bromodeoxyuridine. Cell Tissue Kinet. 1985 Nov;18(6):641–651. doi: 10.1111/j.1365-2184.1985.tb00707.x. [DOI] [PubMed] [Google Scholar]
  136. Siitonen S. M., Kononen J. T., Helin H. J., Rantala I. S., Holli K. A., Isola J. J. Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer. Am J Clin Pathol. 1996 Apr;105(4):394–402. doi: 10.1093/ajcp/105.4.394. [DOI] [PubMed] [Google Scholar]
  137. Slagle B. L., Zhou Y. Z., Birchmeier W., Scorsone K. A. Deletion of the E-cadherin gene in hepatitis B virus-positive Chinese hepatocellular carcinomas. Hepatology. 1993 Oct;18(4):757–762. doi: 10.1002/hep.1840180402. [DOI] [PubMed] [Google Scholar]
  138. Smith K. J., Johnson K. A., Bryan T. M., Hill D. E., Markowitz S., Willson J. K., Paraskeva C., Petersen G. M., Hamilton S. R., Vogelstein B. The APC gene product in normal and tumor cells. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2846–2850. doi: 10.1073/pnas.90.7.2846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  139. Smith K. J., Levy D. B., Maupin P., Pollard T. D., Vogelstein B., Kinzler K. W. Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res. 1994 Jul 15;54(14):3672–3675. [PubMed] [Google Scholar]
  140. Smith M. E., Pignatelli M. The molecular histology of neoplasia: the role of the cadherin/catenin complex. Histopathology. 1997 Aug;31(2):107–111. doi: 10.1046/j.1365-2559.1997.2350845.x. [DOI] [PubMed] [Google Scholar]
  141. Stappert J., Kemler R. A short core region of E-cadherin is essential for catenin binding and is highly phosphorylated. Cell Adhes Commun. 1994 Aug;2(4):319–327. doi: 10.3109/15419069409014207. [DOI] [PubMed] [Google Scholar]
  142. Stoker M., Gherardi E. Regulation of cell movement: the motogenic cytokines. Biochim Biophys Acta. 1991 Apr 16;1072(1):81–102. doi: 10.1016/0304-419x(91)90008-9. [DOI] [PubMed] [Google Scholar]
  143. Su L. K., Vogelstein B., Kinzler K. W. Association of the APC tumor suppressor protein with catenins. Science. 1993 Dec 10;262(5140):1734–1737. doi: 10.1126/science.8259519. [DOI] [PubMed] [Google Scholar]
  144. Sundfør K., Lyng H., Rofstad E. K. Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer. 1998 Sep;78(6):822–827. doi: 10.1038/bjc.1998.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  145. Tabibzadeh S., Kong Q. F., Kapur S., Satyaswaroop P. G., Aktories K. Tumour necrosis factor-alpha-mediated dyscohesion of epithelial cells is associated with disordered expression of cadherin/beta-catenin and disassembly of actin filaments. Hum Reprod. 1995 Apr;10(4):994–1004. doi: 10.1093/oxfordjournals.humrep.a136084. [DOI] [PubMed] [Google Scholar]
  146. Takaishi K., Sasaki T., Kotani H., Nishioka H., Takai Y. Regulation of cell-cell adhesion by rac and rho small G proteins in MDCK cells. J Cell Biol. 1997 Nov 17;139(4):1047–1059. doi: 10.1083/jcb.139.4.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  147. Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol. 1993 Oct;5(5):806–811. doi: 10.1016/0955-0674(93)90029-p. [DOI] [PubMed] [Google Scholar]
  148. Tamura S., Shiozaki H., Miyata M., Kadowaki T., Inoue M., Matsui S., Iwazawa T., Takayama T., Takeichi M., Monden M. Decreased E-cadherin expression is associated with haematogenous recurrence and poor prognosis in patients with squamous cell carcinoma of the oesophagus. Br J Surg. 1996 Nov;83(11):1608–1614. doi: 10.1002/bjs.1800831138. [DOI] [PubMed] [Google Scholar]
  149. Terrés A. M., Pajares J. M., Hopkins A. M., Murphy A., Moran A., Baird A. W., Kelleher D. Helicobacter pylori disrupts epithelial barrier function in a process inhibited by protein kinase C activators. Infect Immun. 1998 Jun;66(6):2943–2950. doi: 10.1128/iai.66.6.2943-2950.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  150. Terrés A. M., Pajares J. M., O'Toole D., Ahern S., Kelleher D. H pylori infection is associated with downregulation of E-cadherin, a molecule involved in epithelial cell adhesion and proliferation control. J Clin Pathol. 1998 May;51(5):410–412. doi: 10.1136/jcp.51.5.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  151. Thomsen L. L., Miles D. W. Role of nitric oxide in tumour progression: lessons from human tumours. Cancer Metastasis Rev. 1998 Mar;17(1):107–118. doi: 10.1023/a:1005912906436. [DOI] [PubMed] [Google Scholar]
  152. Toropainen E., Lipponen P., Syrjänen K. Expression of insulin-like growth factor I (IGF-I) in female breast cancer as related to established prognostic factors and long-term prognosis. Eur J Cancer. 1995;31A(9):1443–1448. doi: 10.1016/0959-8049(94)00466-i. [DOI] [PubMed] [Google Scholar]
  153. Umbas R., Isaacs W. B., Bringuier P. P., Schaafsma H. E., Karthaus H. F., Oosterhof G. O., Debruyne F. M., Schalken J. A. Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 1994 Jul 15;54(14):3929–3933. [PubMed] [Google Scholar]
  154. Van Aken J., Cuvelier C. A., De Wever N., Roels J., Gao Y., Mareel M. M. Immunohistochemical analysis of E-cadherin expression in human colorectal tumours. Pathol Res Pract. 1993 Nov;189(9):975–978. doi: 10.1016/S0344-0338(11)80667-9. [DOI] [PubMed] [Google Scholar]
  155. Van Roy F., Mareel M. Tumour invasion: effects of cell adhesion and motility. Trends Cell Biol. 1992 Jun;2(6):163–169. doi: 10.1016/0962-8924(92)90035-l. [DOI] [PubMed] [Google Scholar]
  156. Veatch A. L., Carson L. F., Ramakrishnan S. Differential expression of the cell-cell adhesion molecule E-cadherin in ascites and solid human ovarian tumor cells. Int J Cancer. 1994 Aug 1;58(3):393–399. doi: 10.1002/ijc.2910580315. [DOI] [PubMed] [Google Scholar]
  157. WILDER R. J. The historical development of the concept of metastasis. J Mt Sinai Hosp N Y. 1956 Sep-Oct;23(5):728–734. [PubMed] [Google Scholar]
  158. Wei W. Z., Fulton A., Winkelhake J., Heppner G. Correlation of natural killer activity with tumorigenesis of a preneoplastic mouse mammary lesion. Cancer Res. 1989 May 15;49(10):2709–2715. [PubMed] [Google Scholar]
  159. Whitlon D. S. E-cadherin in the mature and developing organ of Corti of the mouse. J Neurocytol. 1993 Dec;22(12):1030–1038. doi: 10.1007/BF01235747. [DOI] [PubMed] [Google Scholar]
  160. Wotherspoon A. C. Helicobacter pylori infection and gastric lymphoma. Br Med Bull. 1998;54(1):79–85. doi: 10.1093/oxfordjournals.bmb.a011683. [DOI] [PubMed] [Google Scholar]
  161. Wójciak-Stothard B., Entwistle A., Garg R., Ridley A. J. Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells. J Cell Physiol. 1998 Jul;176(1):150–165. doi: 10.1002/(SICI)1097-4652(199807)176:1<150::AID-JCP17>3.0.CO;2-B. [DOI] [PubMed] [Google Scholar]
  162. Yamashina K., Miller B. E., Heppner G. H. Macrophage-mediated induction of drug-resistant variants in a mouse mammary tumor cell line. Cancer Res. 1986 May;46(5):2396–2401. [PubMed] [Google Scholar]
  163. Young S. D., Hill R. P. Effects of reoxygenation on cells from hypoxic regions of solid tumors: anticancer drug sensitivity and metastatic potential. J Natl Cancer Inst. 1990 Mar 7;82(5):371–380. doi: 10.1093/jnci/82.5.371. [DOI] [PubMed] [Google Scholar]
  164. Young S. D., Marshall R. S., Hill R. P. Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9533–9537. doi: 10.1073/pnas.85.24.9533. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES