Wang Jingya, Pan Wensheng
Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Onco Targets Ther. 2020 Jun 22;13:5779-5793. doi: 10.2147/OTT.S256654. eCollection 2020.
The collagen alpha-3 (VI) chain encoded by the gene is one of the 3 subunits of collagen VI which is a microfibrillar component of the extracellular matrix and is essential for the stable assembly process of collagen VI. The collagen alpha-3 (VI) chain and the cleaved C5 domain fragment, called endotrophin, are highly expressed in a variety of cancers and play a crucial role in cancer progression. The biological functions of endotrophin in tumors can be driven by adipocytes. Studies have demonstrated that endotrophin can directly affect the malignancy of cancer cells through TGF-β-dependent mechanisms, inducing epithelial-mesenchymal transition and fibrosis of the tumor microenvironment. In addition, endotrophin can also recruit macrophages and endothelial cells through chemotaxis to regulate the tumor microenvironment and ultimately promote tumor inflammation and angiogenesis. Furthermore, COL6A3 and endotrophin serve as novel diagnostic and prognostic biomarkers in cancer and contribute to clinical therapeutic applications in the future. In summary, in this review, we discuss the importance of the collagen alpha-3 (VI) chain and endotrophin in cancer progression, the future clinical applications of endotrophin and the remaining challenges in this field.
由该基因编码的胶原蛋白α-3（VI）链是胶原蛋白VI的3个亚基之一，胶原蛋白VI是细胞外基质的微纤维成分，对胶原蛋白VI的稳定组装过程至关重要。胶原蛋白α-3（VI）链和被称为内营养蛋白的裂解C5结构域片段在多种癌症中高度表达，并在癌症进展中起关键作用。内营养蛋白在肿瘤中的生物学功能可由脂肪细胞驱动。研究表明，内营养蛋白可通过TGF-β依赖性机制直接影响癌细胞的恶性程度，诱导上皮-间质转化和肿瘤微环境纤维化。此外，内营养蛋白还可通过趋化作用募集巨噬细胞和内皮细胞，以调节肿瘤微环境并最终促进肿瘤炎症和血管生成。此外，COL6A3和内营养蛋白可作为癌症新型诊断和预后生物标志物，并有助于未来的临床治疗应用。总之，在本综述中，我们讨论了胶原蛋白α-3（VI）链和内营养蛋白在癌症进展中的重要性、内营养蛋白未来的临床应用以及该领域尚存的挑战。
