期刊
INTERNATIONAL JOURNAL OF CANCER
卷 145, 期 2, 页码 503-516出版社
WILEY
DOI: 10.1002/ijc.32121
关键词
KCa3.1; SKP2; RELN; hepatocellular carcinoma
类别
资金
- Innovative Research Groups of National Natural Science Foundation of China [81721091]
- Major program of National Natural Science Foundation of China [91542205]
- National Natural Science Foundation of China [81272675, 81570575, 31470753]
- National ST Major Project [2017ZX10203205]
The intermediate conductance calcium-activated potassium channel (KCa3.1) plays an important role in maintaining intracellular calcium homeostasis and is involved in the tumorigenesis of many human cancers. However, it is unknown whether KCa3.1 plays a role in the genesis of hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide with a very poor prognosis. In our study, we found that the expression of KCa3.1 was significantly elevated in poorly differentiated HCC tissues compared to adjacent noncancerous tissues. In vitro and in vivo experiments showed that KCa3.1 could promote cell proliferation, migration, and invasion of HCC. Mechanistically, KCa3.1 promoted cell cycle progression and migration and invasion of HCC cells by activating S-phase protein kinase 2 (SKP2) to trigger the degradation of p21 and p27 and targeting Reelin (RELN) to induce epithelial-mesenchymal transition (EMT), respectively. Taken together, our results demonstrate that KCa3.1 plays an important role in the genesis and progression of HCC, implying that it might be a promising therapeutic target in HCC.
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