CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling. CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling

We report that loss of CCM3/PDCD10 in fibroblasts induces FAK/Src-paxillin signalling driving actomyosin-dependent mechanotransduction leading to YAP/TAZ signalling. In vivo, loss of CCM3 in fibroblasts drives excessive tissue remodelling leading to the dissemination of breast cancer cells to distant organs. Overall design: Examination of the varying RNA levels in control human vulval cancer-associated fibroblasts versus CCM3-depleted cells

本研究证实，成纤维细胞中CCM3/PDCD10的缺失会诱导黏着斑激酶（Focal Adhesion Kinase）/Src-桩蛋白（paxillin）信号通路活化，该通路介导依赖于肌动球蛋白（actomyosin）的机械转导（mechanotransduction）过程，进而激活YAP/TAZ信号通路。在活体实验中，成纤维细胞内CCM3的缺失会引发过度组织重塑，最终促使乳腺癌细胞向远端器官播散。本实验整体设计为：对比对照组人外阴癌相关成纤维细胞与CCM3缺失细胞的RNA表达水平差异。