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Liu Z , Chen M , Xie LK , Liu T , Zou ZW , Li Y , Chen P , Peng X , Ma C , Zhang WJ , Li PD
CLCA4 inhibits cell proliferation and invasion of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition via PI3K/AKT signaling
Aging (Albany NY). 2018 Oct 11;10(10) :2570-2584
PMID: 30312171 PMCID: PMC6224236 URL: https://www.ncbi.nlm.nih.gov/pubmed/30312171
AbstractCalcium activated Chloride Channel A4 (CLCA4), as a tumor suppressor, was reported to contribute to the progression of several malignant tumors, yet little is known about the significance of CLCA4 in invasion and prognosis of hepatocellular carcinoma (HCC). CLCA4 expression was negatively correlated with tumor size, vascular invasion and TNM stage. Kaplan-Meier analysis showed that CLCA4 was an independent predictor for overall survival (OS) and time to recurrence (TTR). In addition, CLCA4 status could act as prognostic predictor in different risk of subgroups. Moreover, combination of CLCA4 and serum AFP could be a potential predictor for survival in HCC patients. Furthermore, CLCA4 may inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling. Knockdown of CLCA4 significantly increased the migration and invasion of HCC cells and changed the expression pattern of EMT markers and PI3K/AKT phosphorylation. An opposite expression pattern of EMT markers and PI3K/AKT phosphorylation was observed in CLCA4-transfected cells. Additionally, immunohistochemistry and RT-PCR results further confirmed this correlation. Taken together, CLCA4 contributes to migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favourable prognosis of HCC. CLCA4/AFP expression may help to distinguish different risks of HCC patients after hepatectomy.
Notes1945-4589 Liu, Zhao Chen, Mi Xie, Lin-Ka Liu, Ting Zou, Zhen-Wei Li, Yong Chen, Peng Peng, Xin Ma, Charlie Zhang, Wen-Jie Li, Pin-Dong Journal Article United States Aging (Albany NY). 2018 Oct 11. pii: 101571. doi: 10.18632/aging.101571.