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HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1

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机构： [1]Medical School of Guizhou University, Guiyang 550025, China. [2]Shanxi Academy of Advanced Research and Innovation, Taiyuan 030032, China. [3]Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China. [4]Zhongda Hospital, Medical School, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China. [5]Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China. [6]Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201200, China. [7]Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China. [8]Center for Immunology and Hematology, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan 610044, China

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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.© 2023. The Author(s).

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出版当年[2023]版：

大类 | 1 区

生物学

小类 | 2 区细胞生物学

最新[2023]版：

大类 | 1 区

生物学

小类 | 2 区细胞生物学

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第一作者机构： [1]Medical School of Guizhou University, Guiyang 550025, China. [2]Shanxi Academy of Advanced Research and Innovation, Taiyuan 030032, China. [3]Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China.

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