The keratin 17/YAP/IL6 axis contributes to E-cadherin loss and aggressiveness of diffuse gastric cancer
The keratin 17/YAP/IL6 axis contributes to E-cadherin loss and aggressiveness of diffuse gastric cancer
复制标题
角蛋白17/YAP/IL6轴导致E-钙粘蛋白丢失和弥漫性胃癌的侵袭性
DOI：
10.1038/s41388-021-02119-3
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发表时间：
2021-11-29
期刊：
影响因子：
8
通讯作者：
Zhuo, Wei
中科院分区：
文献类型：
--
作者：
Li, Mengjie;Rao, Xianping;Zhuo, Wei
DGC is a particular aggressive malignancy with poor prognosis. Recent omics studies characterized DGC withCDH1/E-cadherin loss and EMT-signatures. However, the underlying mechanisms for maintaining the aggressive behavior and molecular features of DGC remain unclear. Here, we find that intermediate filaments KRT17 is significantly lower in DGC tissues than that in intestinal gastric cancer tissues and associated with poor prognosis of DGC. We demonstrate that downregulation of KRT17 induces E-cadherin loss, EMT changes, and metastasis behaviors of GC cells. Mechanistically, the loss of intermediate filaments KRT17 induces reorganization of cytoskeleton, further activates YAP signaling, and increases IL6 expression, which contributes to the enhanced metastasis ability of GC cells. Together, these results indicate that KRT17/YAP/IL6 axis contributes to maintaining E-cadherin loss, EMT feature, and metastasis of DGC, providing a new insight into the role of aberrant intermediate filaments in DGC malignancy.
