COL6A3, which encodes the alpha(α)3(VI) chain of type VI collagen, is involved in multiple biological functions. Collagen VI, of which COL6A3 is a part, has mechanical roles, cytoprotective functions such as inhibiting apoptosis and oxidative damage, and also regulates cell differentiation and autophagic mechanisms, promoting tumor growth and progression [2].

In epithelial ovarian cancer, high COL6A3 expression is associated with worse overall survival. Cancer-derived exosomes containing COL6A3 enhance tumor dissemination and metastasis, while knockdown of COL6A3 can suppress the aggressiveness of the cancer [1]. In osteosarcoma, knockdown of COL6A3 using siRNA technology inhibits cell proliferation, invasion, and migration, suggesting its role in promoting the malignancy of osteosarcoma through activating the PI3K/AKT pathway [3]. In pancreatic adenocarcinoma, COL6A3 expression in cancer tissues is correlated with negative prognostic factors [4]. In undifferentiated pleomorphic sarcoma, COL6A3 is identified as a prognostic biomarker, predicting overall survival in patients [5].

In conclusion, COL6A3 is crucial for normal tissue function and is implicated in various disease processes, especially in cancer progression and metastasis. Functional studies, including knockdown experiments in different cancer cell lines, have provided insights into its role in promoting tumor malignancy. Understanding COL6A3 may offer potential therapeutic targets for treating related diseases.

References:

1. Ho, Chih-Ming, Yen, Ting-Lin, Chang, Tzu-Hao, Huang, Shih-Hung. 2024. COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer. In International journal of molecular sciences, 25, . doi:10.3390/ijms25158121. https://pubmed.ncbi.nlm.nih.gov/39125689/

2. Di Martino, Alberto, Cescon, Matilde, D'Agostino, Claudio, Merlini, Luciano, Faldini, Cesare. 2023. Collagen VI in the Musculoskeletal System. In International journal of molecular sciences, 24, . doi:10.3390/ijms24065095. https://pubmed.ncbi.nlm.nih.gov/36982167/

3. Guo, Hong-Li, Chen, Gang, Song, Ze-Long, Gao, Xi-Hai, Han, Yu-Xia. 2020. COL6A3 promotes cellular malignancy of osteosarcoma by activating the PI3K/AKT pathway. In Revista da Associacao Medica Brasileira (1992), 66, 740-745. doi:10.1590/1806-9282.66.6.740. https://pubmed.ncbi.nlm.nih.gov/32696868/

4. Svoronos, Christos, Tsoulfas, Georgios, Souvatzi, Maria, Chatzitheoklitos, Efthimios. 2020. Prognostic value of COL6A3 in pancreatic adenocarcinoma. In Annals of hepato-biliary-pancreatic surgery, 24, 52-56. doi:10.14701/ahbps.2020.24.1.52. https://pubmed.ncbi.nlm.nih.gov/32181429/

5. Klein, Jason C, Wang, Lei, Strand, Douglas, Hosler, Gregory A, Hon, Gary C. 2024. Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic sarcoma. In Molecular cancer, 23, 257. doi:10.1186/s12943-024-02168-8. https://pubmed.ncbi.nlm.nih.gov/39548577/