Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Sep;74(5):780–787. doi: 10.1038/bjc.1996.436

Tyrosine phosphorylation of 100-130 kDa proteins in lung cancer correlates with poor prognosis.

M Nishimura 1, K Machida 1, M Imaizumi 1, T Abe 1, T Umeda 1, E Takeshima 1, T Watanabe 1, Y Ohnishi 1, K Takagi 1, M Hamaguchi 1
PMCID: PMC2074703  PMID: 8795582

Abstract

To search for the signalling pathways in lung cancer relevant to its aggressive behaviour, we studied tyrosine phosphorylated proteins in lung cancer cell lines and surgical specimens. We found that the profiles of protein phosphorylation were closely matched among these cell lines and cancer tissues of different histological origins, and 100-130 kDa proteins were the major components of phosphorylated proteins. In surgical specimens, approximately half of the cases showed tyrosine phosphorylation of these proteins in a tumour-specific manner, and phosphorylation of these proteins showed good correlation with the survival length of patients after operation. By immunoprecipitation with specific antibodies, we found that p125FAK, p120 and beta-catenin were the major components of tyrosine-phosphorylated proteins in the surgical specimens. These results suggest that tyrosine phosphorylation of these proteins may play a role in tumour relapse and is available as a clinical marker.

Full text

PDF
780

Images in this article

Selected References

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

  1. Berger M. S., Gullick W. J., Greenfield C., Evans S., Addis B. J., Waterfield M. D. Epidermal growth factor receptors in lung tumours. J Pathol. 1987 Aug;152(4):297–307. doi: 10.1002/path.1711520408. [DOI] [PubMed] [Google Scholar]
  2. Burridge K., Turner C. E., Romer L. H. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol. 1992 Nov;119(4):893–903. doi: 10.1083/jcb.119.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cerny T., Barnes D. M., Hasleton P., Barber P. V., Healy K., Gullick W., Thatcher N. Expression of epidermal growth factor receptor (EGF-R) in human lung tumours. Br J Cancer. 1986 Aug;54(2):265–269. doi: 10.1038/bjc.1986.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dazzi H., Hasleton P. S., Thatcher N., Barnes D. M., Wilkes S., Swindell R., Lawson R. A. Expression of epidermal growth factor receptor (EGF-R) in non-small cell lung cancer. Use of archival tissue and correlation of EGF-R with histology, tumour size, node status and survival. Br J Cancer. 1989 May;59(5):746–749. doi: 10.1038/bjc.1989.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Haeder M., Rotsch M., Bepler G., Hennig C., Havemann K., Heimann B., Moelling K. Epidermal growth factor receptor expression in human lung cancer cell lines. Cancer Res. 1988 Mar 1;48(5):1132–1136. [PubMed] [Google Scholar]
  6. Hamaguchi M., Grandori C., Hanafusa H. Phosphorylation of cellular proteins in Rous sarcoma virus-infected cells: analysis by use of anti-phosphotyrosine antibodies. Mol Cell Biol. 1988 Aug;8(8):3035–3042. doi: 10.1128/mcb.8.8.3035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamaguchi M., Xiao H., Uehara Y., Ohnishi Y., Nagai Y. Herbimycin A inhibits the association of p60v-src with the cytoskeletal structure and with phosphatidylinositol 3' kinase. Oncogene. 1993 Mar;8(3):559–564. [PubMed] [Google Scholar]
  8. Ilić D., Furuta Y., Kanazawa S., Takeda N., Sobue K., Nakatsuji N., Nomura S., Fujimoto J., Okada M., Yamamoto T. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature. 1995 Oct 12;377(6549):539–544. doi: 10.1038/377539a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Kern J. A., Schwartz D. A., Nordberg J. E., Weiner D. B., Greene M. I., Torney L., Robinson R. A. p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res. 1990 Aug 15;50(16):5184–5187. [PubMed] [Google Scholar]
  11. Kinjo M., Oka K., Naito S., Kohga S., Tanaka K., Oboshi S., Hayata Y., Yasumoto K. Thromboplastic and fibrinolytic activities of cultured human cancer cell lines. Br J Cancer. 1979 Jan;39(1):15–23. doi: 10.1038/bjc.1979.3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kornberg L., Earp H. S., Parsons J. T., Schaller M., Juliano R. L. Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase. J Biol Chem. 1992 Nov 25;267(33):23439–23442. [PubMed] [Google Scholar]
  13. Macaulay V. M., Everard M. J., Teale J. D., Trott P. A., Van Wyk J. J., Smith I. E., Millar J. L. Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells. Cancer Res. 1990 Apr 15;50(8):2511–2517. [PubMed] [Google Scholar]
  14. Macauly V. M., Teale J. D., Everard M. J., Joshi G. P., Smith I. E., Millar J. L. Somatomedin-C/insulin-like growth factor-I is a mitogen for human small cell lung cancer. Br J Cancer. 1988 Jan;57(1):91–93. doi: 10.1038/bjc.1988.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Matsuyoshi N., Hamaguchi M., Taniguchi S., Nagafuchi A., Tsukita S., Takeichi M. Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J Cell Biol. 1992 Aug;118(3):703–714. doi: 10.1083/jcb.118.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mayer B. J., Hamaguchi M., Hanafusa H. A novel viral oncogene with structural similarity to phospholipase C. Nature. 1988 Mar 17;332(6161):272–275. doi: 10.1038/332272a0. [DOI] [PubMed] [Google Scholar]
  17. Reynolds A. B., Herbert L., Cleveland J. L., Berg S. T., Gaut J. R. p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors beta-catenin, plakoglobin and armadillo. Oncogene. 1992 Dec;7(12):2439–2445. [PubMed] [Google Scholar]
  18. Reynolds A. B., Roesel D. J., Kanner S. B., Parsons J. T. Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol. 1989 Feb;9(2):629–638. doi: 10.1128/mcb.9.2.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saga S., Hamaguchi M., Hoshino M., Kojima K. Expression of meta-vinculin associated with differentiation of chicken embryonal muscle cells. Exp Cell Res. 1985 Jan;156(1):45–56. doi: 10.1016/0014-4827(85)90260-5. [DOI] [PubMed] [Google Scholar]
  20. Sakai R., Iwamatsu A., Hirano N., Ogawa S., Tanaka T., Mano H., Yazaki Y., Hirai H. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner. EMBO J. 1994 Aug 15;13(16):3748–3756. doi: 10.1002/j.1460-2075.1994.tb06684.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schaller M. D., Borgman C. A., Cobb B. S., Vines R. R., Reynolds A. B., Parsons J. T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. doi: 10.1073/pnas.89.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schneider P. M., Hung M. C., Chiocca S. M., Manning J., Zhao X. Y., Fang K., Roth J. A. Differential expression of the c-erbB-2 gene in human small cell and non-small cell lung cancer. Cancer Res. 1989 Sep 15;49(18):4968–4971. [PubMed] [Google Scholar]
  23. Siegfried J. M. Detection of human lung epithelial cell growth factors produced by a lung carcinoma cell line: use in culture of primary solid lung tumors. Cancer Res. 1987 Jun 1;47(11):2903–2910. [PubMed] [Google Scholar]
  24. Takeshima E., Hamaguchi M., Watanabe T., Akiyama S., Kataoka M., Ohnishi Y., Xiao H. Y., Nagai Y., Takagi H. Aberrant elevation of tyrosine-specific phosphorylation in human gastric cancer cells. Jpn J Cancer Res. 1991 Dec;82(12):1428–1435. doi: 10.1111/j.1349-7006.1991.tb01816.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Veale D., Ashcroft T., Marsh C., Gibson G. J., Harris A. L. Epidermal growth factor receptors in non-small cell lung cancer. Br J Cancer. 1987 May;55(5):513–516. doi: 10.1038/bjc.1987.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weiner D. B., Nordberg J., Robinson R., Nowell P. C., Gazdar A., Greene M. I., Williams W. V., Cohen J. A., Kern J. A. Expression of the neu gene-encoded protein (P185neu) in human non-small cell carcinomas of the lung. Cancer Res. 1990 Jan 15;50(2):421–425. [PubMed] [Google Scholar]
  27. Zachary I., Sinnett-Smith J., Rozengurt E. Bombesin, vasopressin, and endothelin stimulation of tyrosine phosphorylation in Swiss 3T3 cells. Identification of a novel tyrosine kinase as a major substrate. J Biol Chem. 1992 Sep 25;267(27):19031–19034. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES