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The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma
Author(s) -
Du Yehui,
Song Wenfeng,
Chen Jian,
Chen Hao,
Xuan Zefeng,
Zhao Long,
Chen Jun,
Jin Cheng,
Zhou Mengqiao,
Tuo Biguang,
Zhao Yongchao,
Zheng Shusen,
Song Penghong
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32121
Subject(s) - cancer research , skp2 , metastasis , carcinogenesis , reelin , cell growth , hepatocellular carcinoma , biology , cell , kinase , epithelial–mesenchymal transition , cancer , medicine , microbiology and biotechnology , ubiquitin , ubiquitin ligase , biochemistry , genetics , extracellular matrix , gene
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.