Integrin alpha 7 correlates with poor clinical outcomes, and it regulates cell proliferation, apoptosis and stemness via PTK2-PI3K-Akt signaling pathway in hepatocellular carcinoma

This study aimed to evaluate the correlation of integrin alpha 7 (ITGA7) with clinical outcomes and its effect on cell activities as well as stemness in hepatocellular carcinoma (HCC). HCC tumor tissues and paired adjacent tissues from 90 HCC patients were obtained and ITGA7 expression was detected using immunohistochemistry assay. Cellular experiments were conducted to examine the effect of ITGA7 on cell activities, astemness via ITGA7 ShRNA transfection, and compensation experiments were further performed to test whether ITGA7 functioned via regulating PTK2-PI3K-AKT signaling pathway. ITGA7 was overexpressed in tumor tissues compared with paired adjacent tissues and its high expression was correlated with larger tumor size, vein invasion and advanced Barcelona Clinic Liver Cancer stage, and it also independently predicted worse overall survival in HCC patients. In cellular experiments, ITGA7 was upregulated in SMMC-7721, Hep G2, HuH-7 and BEL-7404 cell lines compared with normal human liver cells HL-7702. ITGA7 knockdown suppressed cell proliferation but promoted apoptosis, and it also downregulated CSCs markers (CD44, CD133 and OCT-4) as well as PTK2, PI3K and AKT expressions in SMMC-7721 and Hep G2 cell lines. ITGA7 overexpression promoted cell proliferation but inhibited apoptosis, and it also upregulated CSCs markers in HL-7702 cells. Further compensation experiments verified that ITGA7 regulated cell proliferation, apoptosis and CSCs markers via PTK2-PI3K-Akt signaling pathway. ITGA7 negatively associates with clinical outcomes in HCC patients, and it regulates cell proliferation, apoptosis and CSCs markers via PTK2-PI3K-Akt signaling pathway.