HER4 promotes the progression of colorectal cancer by promoting epithelial-mesenchymal transition

Colorectal cancer (CRC) remains one of the most common cancer types worldwide. A few previous studies have examined whether HER4 may promote the progression of CRC. The present study examined the associations among the expression levels of members of the HER family, and investigated the potential mechanism underlying the function of HER4 in CRC cells. Immunohistochemistry analysis was conducted to detect the expression levels of HER family members in patients with CRC. HER4 expression was knocked down using short hairpin RNA in HCT116 cells, and confirmed by quantitative PCR and western blotting. The proliferation and adhesion of CRC cells were analyzed by CCK-8 assays and adhesive assays, respectively. Flow cytometry was used to measure cell apoptosis. Western blotting and immunofluorescence staining in CRC cells were performed to identify proteins related to epithelial-mesenchymal transition. The proportion of patients with CRC presenting positive expression of the HER family members epidermal growth factor receptor (EGFR), HER2, HER3 and HER4 were 72.1, 45.2, 43.8 and 34.2%, respectively. No relationship was found between HER4 and EGFR, HER2 or HER3 expression. Higher expression of HER4 was positively associated with lymph node metastasis (P=0.039). In the present study, HER4 expression was found to be associated with an unfavorable clinical outcome in patients with CRC (P(logrank)=0.020). Cell proliferation was inhibited, and apoptosis was increased following HER4 knockdown. Furthermore, HER4 knockdown increased the expression of E-cadherin and decreased the expressions of N-cadherin and vimentin (P<0.05). HER4 expression was found to be unrelated to other HER family members. In the present study, positive expression of HER4 promoted the progression of CRC through epithelial-mesenchymal transition.