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HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1.
Han, Xiaoqi; Jiang, Siyuan; Gu, Yinmin; Ding, Lihua; Zhao, Enhao; Cao, Dongxing; Wang, Xiaodong; Wen, Ya; Pan, Yongbo; Yan, Xin; Duan, Liqiang; Sun, Minxuan; Zhou, Tao; Liu, Yajuan; Hu, Hongbo; Ye, Qinong; Gao, Shan.
Affiliation
  • Han X; Medical School of Guizhou University, Guiyang, 550025, China.
  • Jiang S; Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030032, China.
  • Gu Y; Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.
  • Ding L; Zhongda Hospital, Medical School, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.
  • Zhao E; Zhongda Hospital, Medical School, Advanced Institute for Life and Health, Southeast University, Nanjing, 210096, China.
  • Cao D; Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Collaborative Innovation Center for Cancer Medicine, Beijing, 100850, China.
  • Wang X; Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 201200, China.
  • Wen Y; Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 201200, China.
  • Pan Y; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.
  • Yan X; Medical School of Guizhou University, Guiyang, 550025, China.
  • Duan L; Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030032, China.
  • Sun M; Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030032, China.
  • Zhou T; Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030032, China.
  • Liu Y; Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030032, China.
  • Hu H; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.
  • Ye Q; Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.
  • Gao S; Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030032, China.
Cell Death Dis ; 14(5): 327, 2023 05 16.
Article in En | MEDLINE | ID: mdl-37193711
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Epithelial-Mesenchymal Transition Limits: Humans Language: En Journal: Cell Death Dis Year: 2023 Document type: Article Affiliation country: China Country of publication: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Epithelial-Mesenchymal Transition Limits: Humans Language: En Journal: Cell Death Dis Year: 2023 Document type: Article Affiliation country: China Country of publication: United kingdom