PDF(Pubmed)
Abstract：
Collagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic function for mutant collagens is undefined. Here we identify COL11A1 mutations in 66 of 100 cutaneous squamous cell carcinomas (cSCCs), the second most common U.S. cancer, concentrated in a triple helical region known to produce trans-dominant collagens. Analysis of COL11A1 and other collagen genes found that they are mutated across common epithelial malignancies. Knockout of mutant COL11A1 impairs cSCC tumorigenesis in vivo. Compared to otherwise genetically identical COL11A1 wild-type tissue, gene-edited mutant COL11A1 skin is characterized by induction of β1 integrin targets and accelerated neoplastic invasion. In mosaic tissue, mutant COL11A1 cells enhanced invasion by neighboring wild-type cells. These results suggest that specific collagens are commonly mutated in cancer and that mutant collagens may accelerate this process.
摘要：
胶原蛋白是体内最丰富的蛋白质，包括基底膜和基质，通过它们发生癌性侵袭；然而，突变胶原的肿瘤前功能尚不明确。在这里，我们确定了100个皮肤鳞状细胞癌（cSCC）中66个的COL11A1突变，美国第二常见的癌症，集中在已知产生反式显性胶原蛋白的三螺旋区域。对COL11A1和其他胶原蛋白基因的分析发现，它们在常见的上皮恶性肿瘤中发生突变。突变COL11A1基因敲除在体内损害cSCC肿瘤发生。与其他基因相同的COL11A1野生型组织相比，基因编辑突变体COL11A1皮肤的特征是诱导β1整合素靶标和加速的肿瘤侵袭。在马赛克组织中，突变的COL11A1细胞增强了邻近野生型细胞的侵袭。这些结果表明，特定的胶原蛋白通常在癌症中发生突变，突变的胶原蛋白可能会加速这一过程。
