Open AccessRole for calcium‐activated potassium channels (BK) in migration control of human hepatocellular carcinoma cells
Author(s) -
He Yuan,
Lin Yingying,
He Fei,
Shao Lijuan,
Ma Wei,
He Fei
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16918
Subject(s) - bk channel , cancer research , metastasis , potassium channel , chemistry , cell migration , cell , calcium activated potassium channel , vimentin , microbiology and biotechnology , biology , cancer , medicine , endocrinology , immunology , biochemistry , immunohistochemistry
Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death worldwide. Its high metastasis rate is significantly correlated with poor patient prognosis. Elucidating the molecular mechanism underlying HCC metastasis is essential for HCC treatment. Owing to their high conductance, large‐conductance calcium‐activated potassium channels (BK channels) play a critical role in the control of membrane potential and have repeatedly been proposed as potential targets for cancer therapy. Emerging evidence suggests that BK channels are involved in the progression of cancer malignancies. The present study investigated the role of BK channels in mediating the hypoxia‐stimulated migration of HCC cells both in vitro and in vivo in the absence and presence of various BK channels modulators. We found that BK channels were functionally expressed on the membranes of the SMMC‐7721 and Huh7 HCC cell lines. Furthermore, blockage or activation of BK channels on the surface of HCC cells correspondingly inhibited or promoted HCC cell proliferation, migration and invasion in hypoxia conditions, with altered expression and distribution of cell‐cell adhesion molecule E‐cadherin and typical marker of mesenchymal cells, Vimentin, but not N‐cadherin. Hypoxia conditions did not alter BK channels expression but increased its open probability. Moreover, BK channels blocker IbTX significantly inhibited HCC cell remote colonization in HCC cell xenografted mice. In conclusion, the results of this study suggest that blocking BK channels offers an attractive strategy for treating HCC.