罗亚
磷酸化
转移
上皮-间质转换
癌症研究
激酶
细胞生物学
肌动蛋白解聚因子
结直肠癌
化学
生物
癌症
信号转导
生物化学
细胞
肌动蛋白细胞骨架
遗传学
细胞骨架
作者
Xiaoqi Han,Siyuan Jiang,Yinmin Gu,Lihua Ding,Enyue Zhao,Dejun Cao,Xiaodong Wang,Ya Wen,Yongbo Pan,Xin Yan,Liqiang Duan,Min Sun,Tao Zhou,Yajuan Liu,Hongbo Hu,Qinong Ye,Shan Gao
标识
DOI:10.1038/s41419-023-05849-2
摘要
Abstract Epithelial-mesenchymal transition (EMT) is associated with the invasive and metastatic phenotypes in colorectal cancer (CRC). However, the mechanisms underlying EMT in CRC are not completely understood. In this study, we find that HUNK inhibits EMT and metastasis of CRC cells via its substrate GEF-H1 in a kinase-dependent manner. Mechanistically, HUNK directly phosphorylates GEF-H1 at serine 645 (S645) site, which activates RhoA and consequently leads to a cascade of phosphorylation of LIMK-1/CFL-1, thereby stabilizing F-actin and inhibiting EMT. Clinically, the levels of both HUNK expression and phosphorylation S645 of GEH-H1 are not only downregulated in CRC tissues with metastasis compared with that without metastasis, but also positively correlated among these tissues. Our findings highlight the importance of HUNK kinase direct phosphorylation of GEF-H1 in regulation of EMT and metastasis of CRC.
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