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Int J Cancer. 2019 Jan 10. doi: 10.1002/ijc.32121. [Epub ahead of print]

The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma.

Du Y1,2,3,4, Song W1,2,3,4, Chen J1,2,3,4, Chen H1,2,3,4, Xuan Z1,2,3,4, Zhao L1,2,3,4, Chen J1,2,3,4, Jin C1,2,3,4, Zhou M1,2,3,4, Tuo B5, Zhao Y1,2,6, Zheng S1,2,3,4, Song P1,2,3,4.

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Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University.
NHFPC Key Laboratory of Combined Multi-organ Transplantation.
Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases.
Department of Gastroenterology, Affiliated Hospital of Zunyi Medical College, Zunyi, 563003, China.
Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310029, China.


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 this study, we found that the expression of KCa3.1 was significantly elevated in poorly differentiated HCC tissues compared with 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. This article is protected by copyright. All rights reserved.


Hepatocellular carcinoma; KCa3.1; RELN; SKP2


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