Hong Xiaoshan, Wen Bin, Zhang Huaming, Li Yuhan, Wu Hengying, Zhao Wei, Luo Xiping
Department of Gynecology, Guangdong Women and Children Hospital, Guangzhou, Guangdong 510010, P.R. China.
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
Exp Ther Med. 2021 Apr;21(4):402. doi: 10.3892/etm.2021.9833. Epub 2021 Feb 25.
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.
1型激活素A受体C（ALK7）及其配体节点生长分化因子（NODAL）在癌细胞中发挥多种作用，包括调节癌症侵袭、迁移和凋亡。NODAL通过激活ALK7促进乳腺癌细胞凋亡；然而，子宫内膜癌（EC）中ALK7和NODAL的表达及其在EC细胞中的作用和潜在机制尚未完全明确。本研究旨在明确NODAL和ALK7在EC中的表达及其潜在机制。通过逆转录定量PCR和蛋白质印迹法检测ALK7和NODAL的表达水平。进行细胞转染以过表达NODAL或干扰ALK7。分别通过细胞计数试剂盒-8、Transwell和伤口愈合实验检测细胞增殖、侵袭和迁移。通过流式细胞术检测细胞凋亡，并通过蛋白质印迹法检测凋亡相关蛋白的表达水平。与正常子宫内膜细胞相比，EC细胞系中NODAL和ALK7的表达水平显著降低。与过表达阴性对照（Ov-NC）组相比，NODAL过表达抑制了EC细胞增殖、侵袭和迁移，并促进了EC细胞凋亡。此外，与Ov-NC组相比，NODAL过表达显著提高了EC细胞中ALK7的表达水平。ALK7逆转了NODAL过表达介导的对EC细胞增殖、侵袭和迁移的抑制以及对EC细胞凋亡的促进作用。本研究表明，NODAL通过激活ALK7抑制EC细胞增殖、侵袭和迁移，并促进EC细胞凋亡。
