Table 1. Sec proteins in human cancer.
Protein | Study | Tumor entity | No. of patients | Animal model | Cell lines | Findings |
---|---|---|---|---|---|---|
Sec61γ | Lu et al.85 | Glioblastoma | N=59 | / | H80, HeLa | SEC61G is amplified and overexpressed in glioblastomas; SEC61G silencing suppresses cell growth and induces apoptosis; ER stress induces SEC61G expression |
Sec62 | Jung et al.88 | Prostate cancer | N=22 | / | PC3, U145, DU145MN1 | SEC62 copy-number gains in 50% of all prostate cancer samples+increased Sec62 protein level; however, copy-number gain in patients with lower risk of and longer time to progression |
Greiner et al.89 | 55 different tumor entities | N=2071 | / | DU145, PC3, LNCaP | SEC62 silencing sensitizes DU145, PC3 and LNCaP cells to thapsigargin treatment; correlation of thapsigargin sensitivity with SEC62 expression in DU145, PC3 and LNCaP cells; 72% of all tumors show SEC62 expression; SEC62 overexpression in tumor tissue compared with healthy tissue of the same organ in lung cancer (93–97%) and thyroid cancer (87–100%); SEC62 silencing reduces the migration of all tested cell lines | |
Greiner et al.94 | Prostate cancer | N=32 | / | A549, H1299, HT1080, TX3868, PC3 | SEC62 overexpression in the majority of prostate cancer cases correlating with the Gleason score | |
Linxweiler et al.90 | NSCLC thyroid cancer | N=70 N=10 | / / | A549, BC01, BHT101, ML1, HEK293 | SEC62 overexpression in tumor tissue compared with healthy lung tissue; high expression levels correlate lymph node metastases and poor tumor differentiation; SEC62 silencing inhibits the migration of NSCLC cells; increased Sec62 protein (40%) and mRNA (60%) levels in thyroid cancer compared with tumor-free tissue; SEC62 silencing inhibits the migration of BC01, BHT101 and ML1 cells, and sensitizes the cells to thapsigargin-induced ER stress; SEC62 overexpression stimulates the migration of HEK293 cells | |
Weng et al.93 | HCC | N=110 | / | / | High SEC62 expression in PBMCs correlates with reduced recurrent-free survival; Sec62 as an independent predictor of HCC recurrence | |
Linxweiler et al.68 | NSCLC | N=70 | / | PC3, HeLa, A549, BC01, BHT101, ML1, HEK293 | High SEC62 expression correlates with a poorer OS; effect of SEC62 silencing on tumor cell migration and ER stress tolerance can be mimicked by CaM anatgonists; SEC62 overexpression in HEK293 cells increases ER stress tolerance | |
Hagerstrand et al.102 | 26 different tumor entities | N=3131 | C.Cg/AnNTac-Foxn1nunu mice | T47D, HCC1937, H3255, HCC95, H1819, H26, TE6, RPMI8226, Fu-Ov-O1, COLO320, MCF7, MDA-MB-231, ZR75-1, HMEC, HCC364, DLD1, HMLE | 3q26 amplification: 22% of tumor samples (43.7% in ovarian cancer, 31.7% in breast cancer, 31.2% in non-small-cell lung cancer). 3q26-encoded SEC62 is required for the proliferation of celll lines with 3q26 amplification; SEC62 overexpression in HMLE cells induces subcutaneous tumor growth in C.Cg/AnNTac-Foxn1nunu mice; SEC62 expression level correlates wtih 3q26 amplification; SEC62 as a tumor-driver gene of the 3q26 region | |
Wemmert et al.92 | HNSCC | N=35 | / | / | High Sec62 protein level is associated with poorer OS and PFS | |
Linxweiler et al.91 | Cervical cancer | N=107 | / | HeLa, MCF7 | Stepwise increase in SEC62 expression depending on the severity of dysplasia with the highest expression in invasive cervical cancer; SEC62 silencing inhibits and SEC62 overexpression stimulates the migration of cervical cancer cells | |
Sec63 | Mori et al.82 | Gastric cancer CRC | N=16 N=43 | / | / | Frameshift mutations of the SEC63 gene due to microsatellite instability in 37.5% of gastric cancers and 48.8% of colorectal cancers |
Schulmann et al.83 | HNPCC-associated SBC | N=17 | / | / | Frameshift mutations of the SEC63 gene due to microsatellite instaibility in 56% of HNPCC-associated small-bowel cancers | |
Casper et al.84 | HCC | N=1 | BXD mice | / | Microsatellite instability in the SEC63 gene in the tested HCC case; correlation of low hepatic SEC63 expression with decreased apoptosis and increased proliferation rate in the mouse model |
Abbreviations: CRC, colorectal cancer; HCC, hepatocellular cancer; HMLE, human mammary epithelial; HNSCC, head and neck squamous cell carcinoma; HNPCC, hereditary non-polyposis colorectal cancer; NSCLC, non-small-cell lung cancer; OS, overall survival, PBMC, peripheral blood mononuclear cell; PFS, progression-free survival, SBC, small-bowel cancer; SEC61G, Sec61γ-coding gene.