Biological effects of NODAL on endometrial cancer cells and its underlying mechanisms

Abstract

Activin A receptor type 1C (ALK7) and its ligand nodal growth differentiation factor (NODAL) serve numerous roles in cancer cells, including regulating cancer invasion, migration and apoptosis. NODAL promotes breast cancer cell apoptosis by activating ALK7; however, ALK7 and NODAL expression in endometrial cancer (EC), as well as their effects and underlying mechanisms in EC cells, are not completely understood. The present study aimed to characterize the expression of NODAL and ALK7 in EC, as well as the underlying mechanisms. The expression levels of ALK7 and NODAL were detected via reverse transcription-quantitative PCR and western blotting. Cell transfection was performed to overexpress NODAL or interfere ALK7. Cell proliferation, invasion and migration were detected via Cell Counting Kit-8, Transwell and wound healing assays, respectively. Flow cytometry was performed to detect cell apoptosis and western blotting was conducted to detect the expression levels of apoptosis-related proteins. NODAL and ALK7 expression levels were significantly decreased in EC cell lines compared with normal endometrial cells. NODAL overexpression inhibited EC cell proliferation, invasion and migration, and promoted EC cell apoptosis compared with the overexpression-negative control (Ov-NC) group. Moreover, NODAL overexpression significantly increased ALK7 expression levels in EC cells compared with the Ov-NC group. ALK7 reversed NODAL overexpression-mediated inhibition of EC cell proliferation, invasion and migration, and promotion of EC cell apoptosis. The present study indicated that NODAL inhibited EC cell proliferation, invasion and migration, and promoted EC cell apoptosis by activating ALK7.

Identification of VEGFs-related gene signature for predicting microangiogenesis and hepatocellular carcinoma prognosis

“…It plays a role in physiological AGING processes such as embryonic development, tissue remodeling and stem cell maintenance [60]. However, NODAL are highly expressed in several malignant tumors, such as melanoma, breast cancer, gastric cancer, HCC, etc., and negatively correlates with the degree of differentiation, clinical stage, metastasis, and prognosis of the tumors [61][62][63]. NODAL is an important component of the TGF-β signaling pathway which enhances the proliferation, migration, and invasion of HCC cells by promoting the phosphorylation of Smad3 and the expression of Snail, drug resistance, and epithelial-mesenchymal transition (EMT) [64].…”