Col6a1, encoding the alpha 1 chain of collagen VI, is crucial for maintaining tissue integrity in the musculoskeletal system and other tissues. Collagen VI has mechanical roles, cytoprotective functions inhibiting apoptosis and oxidative damage, and is involved in regulating cell differentiation and autophagic mechanisms [2].

In osteosarcoma, COL6A1 is commonly upregulated, especially in lung metastasis tissues, promoting cell migration and invasion by suppressing the STAT1 pathway. Overexpression of COL6A1 interacts with SOCS5 to suppress STAT1 expression and activation, and exosomal COL6A1 from osteosarcoma cells can convert normal fibroblasts to cancer-associated fibroblasts, which promote metastasis [1]. In bladder cancer, COL6A1 is downregulated and overexpression suppresses cell viability, migration, and invasion while promoting apoptosis, with its expression positively correlated with FBN1 [3]. In pancreatic cancer, COL6A1 promotes metastasis and predicts poor prognosis, as knockdown of COL6A1 in a metastatic cell line reduces migration and invasion [4]. In osteoarthritis, COL6A1 promotes osteoclast differentiation and formation by activating the EPAC/RAP1 signaling axis, and its knockdown can slow OA progression in mouse models [5].

In conclusion, Col6a1 plays diverse and significant roles in multiple biological processes and disease conditions. Through studies in various disease models, it is evident that Col6a1 is involved in processes like cancer metastasis, cell survival, and tissue remodeling in osteoarthritis. These findings enhance our understanding of the underlying mechanisms in these diseases and may potentially guide the development of targeted therapies.

References:

1. Zhang, Ying, Liu, Zhaoyong, Yang, Xia, Lin, Suxia, Yun, Jing-Ping. 2021. H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts. In Theranostics, 11, 1473-1492. doi:10.7150/thno.51245. https://pubmed.ncbi.nlm.nih.gov/33391546/

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. Yang, Tineng, Peng, Xiaoyang, Huang, Xi, Cao, Peng, Chen, Hualei. 2024. COL6A1 Inhibits the Malignant Development of Bladder Cancer by Regulating FBN1. In Cell biochemistry and biophysics, , . doi:10.1007/s12013-024-01573-6. https://pubmed.ncbi.nlm.nih.gov/39365515/

4. Owusu-Ansah, Kwabena Gyabaah, Song, Guangyuan, Chen, Ronggao, Jiang, Donghai, Zheng, Shusen. 2019. COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer. In International journal of oncology, 55, 391-404. doi:10.3892/ijo.2019.4825. https://pubmed.ncbi.nlm.nih.gov/31268154/

5. Xu, Qu, Feng, Gangning, Tang, Zhiqun, Ma, Long, Jin, Qunhua. . Mechanistic study of COL6A1-mediated subchondral bone remodeling in osteoarthritis via the EPAC/RAP1 axis. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39, e70473. doi:10.1096/fj.202402818RR. https://pubmed.ncbi.nlm.nih.gov/40143596/