Collagens comprise a large, diverse family of proteins that are abundantly expressed throughout most tissues. As a main component of the extracellular matrix (ECM), it is becoming increasingly appreciated how vital collagens are to tumor development, progression, and metastasis.COL6A3, which encodes the alpha 3 chain of type VI collagen, is a unique member of the collagen family that encodes a C-terminal peptide with powerful signaling capabilities, named endotrophin (ETP). Expression ofCOL6A3is required for the survival, migration, and invasion of many cancer cell lines, including breast, bladder, liver, and colorectal cancers. ETP, which was originally discovered to be enriched in the adipocytes of mammary tumors, is a powerful oncopeptide that can alter signaling of tumor and stromal cells. ETP has greater signaling potential than the parentalCOL6A3as it can induce EMT and promote chemoresistance, metastasis, and stemness in an TGF-β-like manner. ETP can also function independently of TGF-β to recruit endothelial cells and macrophages. In this review, we examine the molecular implications ofCOL6A3and ETP expression and their effects on tumor growth, metastasis, and therapeutic response. Finally, we speculate on the potential of serum ETP as a prognostic biomarker in both carcinomas and sarcomas. In summary,COL6A3and ETP are powerful drivers of tumor growth that have potential as noninvasive diagnostic and prognostic tools for the clinical management of cancer.
胶原蛋白是一个庞大且多样化的蛋白质家族，在大多数组织中广泛表达。作为细胞外基质的主要成分，胶原蛋白在肿瘤发生、进展和转移过程中的关键作用日益受到重视。COL6A3基因编码VI型胶原蛋白的α3链，是胶原蛋白家族中独特的成员，其编码的C末端肽段具有强大的信号传导能力，被命名为内脂素（ETP）。COL6A3的表达对多种癌细胞系（包括乳腺癌、膀胱癌、肝癌和结直肠癌）的存活、迁移和侵袭至关重要。最初发现ETP在乳腺肿瘤的脂肪细胞中富集，它是一种强效的肿瘤肽，能够改变肿瘤细胞和基质细胞的信号传导。相较于母体COL6A3，ETP具有更强的信号传导潜力，能够以类似TGF-β的方式诱导上皮-间质转化，并促进化疗耐药、转移和干细胞特性。ETP也可独立于TGF-β发挥作用，招募内皮细胞和巨噬细胞。本综述探讨了COL6A3和ETP表达的分子意义及其对肿瘤生长、转移和治疗反应的影响。最后，我们探讨了血清ETP作为癌和肉瘤预后生物标志物的潜力。总之，COL6A3和ETP是肿瘤生长的重要驱动因子，有望成为癌症临床管理中无创诊断和预后评估的潜在工具。
The Role ofCOL6A3in Tumorigenesis, Metastasis, Diagnosis, and Disease Management
肿瘤(癌症)患者之家