Na+/H+ exchanger 1, Na+/Ca2+ exchanger 1 and calmodulin complex regulates interleukin 6-mediated cellular behavior of human hepatocellular carcinoma

Carcinogenesis
Jingyu XuBiguang Tuo

Abstract

Interleukin 6 (IL6) is a key cytokine involved in the development and progression of inflammation-associated hepatocellular carcinoma (HCC). However, the mechanisms of IL6 action on HCC remain largely unknown. Proton and Ca(2+) are two intracellular messenger ions, which are believed to play a central role in tumorigenesis and tumor progression. In this study, we found that IL6 stimulation markedly increased intracellualr pH recovery rates of human HCC cells, Huh7 and HepG2, after NH4Cl acidification, and the NH4Cl acidification induced transient intracellular Ca(2+) increases in the HCC cells. The inhibition of Na(+)/H(+) exchanger 1 (NHE1), Na(+)/Ca(2+) exchanger 1 (NCX1) and calmodulin (CaM) inhibited the IL6 stimulation-induced intracellular pH recovery increases and NH4Cl acidification-induced intracellular Ca(2+) increases. IL6 stimulation also induced the structural interaction of NHE1, NCX1 and CaM proteins. The protein expression levels of NHE1, NCX1 and CaM in native human HCC tissues were markedly higher than those in normal liver tissues. IL6 upregulated the expressions of NHE1, NCX1 and CaM in Huh7 and HepG2 cells. NHE1, NCX1 and CaM mediated the promotion of IL6 on the proliferation, migration and invasion of Huh7...Continue Reading

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Citations

Jul 30, 2017·Proteomics·Tandekile Lubelwana HafverCathrine Rein Carlson
Oct 20, 2018·Journal of Experimental & Clinical Cancer Research : CR·Xiudong GuanWang Jia
Jan 29, 2019·World Journal of Gastroenterology : WJG·Qiu-Shi LiaoRui Xie
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Sep 4, 2020·Biomolecules·Barbora ChovancovaOlga Krizanova
Sep 29, 2019·Biochemical and Biophysical Research Communications·Shin Young HyunJune-Won Cheong

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