| Autor: |
Xiaoqi Han, Siyuan Jiang, Yinmin Gu, Lihua Ding, Enhao Zhao, Dongxing Cao, Xiaodong Wang, Ya Wen, Yongbo Pan, Xin Yan, Liqiang Duan, Minxuan Sun, Tao Zhou, Yajuan Liu, Hongbo Hu, Qinong Ye, Shan Gao |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Death and Disease, Vol 14, Iss 5, Pp 1-10 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-4889 |
| DOI: |
10.1038/s41419-023-05849-2 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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