HGF induces oncoprotein HCCR-1 expression through the Wnt/β-catenin pathway in gastric cancer

Human cervical cancer oncogene (HCCR)-1, previously identified in cervical cancer and its cell lines, has been reported to play an important role in tumor progression in several cancers as a suppressor of apoptosis. However, the role of HCCR-1 in the tumorigenesis of stomach cancer has not been identified. This study examined the role of HCCR-1 as a suppressor of apoptosis during tumorigenesis in gastric cancer, along with its possible regulatory pathway.

We employed several techniques including western blotting, semiquantitative reverse transcription polymerase chain reaction, diphenyltetrazolium bromide assay, chromatin immunoprecipitation assay, fluorescence-activated cell sorting, and HCCR-1 knockdown with short hairpin RNA to elucidate the role of HCCR-1.

We observed that hepatocyte growth factor (HGF) upregulated HCCR-1 expression. In addition, the expression levels of β-catenin, T cell factor-1 (TCF1), and B-cell lymphoma 2 (bcl2) were increased, whereas that of tumor protein 53 (p53) was decreased following HGF treatment. HCCR-1 knockdown in NUGC-3 and MKN-28 cells decreased the expression of TCF1 and phosphorylated β-catenin and increased the binding activity on the binding site of the HCCR-1 promoter. This identifies the possible involvement of the Wnt/β-catenin pathway in HGF-induced HCCR-1 regulation. We also confirmed the role of HCCR-1 in HGF-induced anti-apoptotic activity. p53 protein expression was increased, whereas that of bcl2 was decreased with HGF treatment in HCCR-1 knockdown cells, while the apoptotic activity was increased.

Our study suggests the anti-apoptotic activity of HGF-induced HCCR-1 expression and that HGF may regulate HCCR-1 via TCF1/β-catenin in stomach cancer.