CMTM6靶向结合HER2促进胃癌细胞增殖、侵袭、迁移和抑制细胞凋亡

张丹; 陈静

doi:10.13406/j.cnki.cyxb.003614

重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (11) : 1402 -1407. DOI: 10.13406/j.cnki.cyxb.003614

基础研究

CMTM6靶向结合HER2促进胃癌细胞增殖、侵袭、迁移和抑制细胞凋亡

张丹 ¹ ,
陈静 ²

作者信息 +

CKLF-like MARVEL transmembrane domain-containing 6 promotes the proliferation，invasion，and migration of gastric cancer cells and inhibits apoptosis through targeted binding to human epidermal growth factor receptor 2

Dan Zhang ¹ ,
Jing Chen ²

Author information +

文章历史 +

PDF (2275K)

摘要

目的探讨趋化素因子超家族6（CKLF-like MARVEL transmembrane domain-containing 6，CMTM6）靶向人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）对胃癌细胞增殖、侵袭、迁移和凋亡的影响及作用机制。方法采用RT-qPCR和Western blot检测CMTM6在胃癌组织、癌旁正常组织和胃癌细胞中的表达水平；在AGS和BGC-823细胞中转染sh-NC和sh-CMTM6后，分别采用CCK8、Transwell和流式细胞术检测细胞增殖、侵袭和迁移，以及凋亡情况。免疫共沉淀（Co-Immunoprecipitation，Co-IP）检测CMTM6和HER2结合情况，放线菌酮（cycloheximide，CHX）检测低表达CMTM6对HER2蛋白稳定性的影响。结果 CMTM6 mRNA和蛋白在胃癌组织中的表达水平明显高于癌旁正常组织，差异有统计学意义。低表达CMTM6能够明显抑制AGS和BGC-823细胞的增殖、侵袭和迁移，促进细胞凋亡，差异有统计学意义；过表达CMTM6能够显著促进AGS和BGC-823细胞的增殖、侵袭和迁移，抑制细胞凋亡，差异有统计学意义。Co-IP显示CMTM6和HER2存在结合，低表达CMTM6能够显著抑制HER2蛋白的表达，同时降低HER2蛋白稳定性，差异有统计学意义。在AGS和BGC-823细胞中共转染LV-CMTM6和sh-HER2后，能够逆转过表达CMTM6对AGS和BGC-823细胞增殖、侵袭、迁移和凋亡的影响。结论 CMTM6在胃癌组织和胃癌细胞中显著高表达，CMTM6能够靶向结合HER2，促进HER2蛋白的稳定性，进而促进胃癌细胞的增殖、侵袭和迁移，以及抑制胃癌细胞的凋亡。

Abstract

Objective To investigate the effect and mechanism of action of CKLF-like MARVEL transmembrane domain-containing6（CMTM6） targeting human epidermal growth factor receptor 2（HER2） on the proliferation，invasion，migration，and apoptosis of gastric cancer cells. Methods RT-qPCR and Western blot were used to measure the expression level of CMTM6 in gastric cancer tissue，normal paracancerous tissue，and gastric cancer cells. After AGS and BGC-823 cells were transfected with sh-NC and sh-CMTM6，CCK8 assay，Transwell assay，and flow cytometry were used to detect cell proliferation，invasion，migration，and apoptosis. Co-immunoprecipitation（Co-IP） was used to detect the binding between CMTM6 and HER2，and cycloheximide（CHX） was used to investigate the effect of low-expression CMTM6 on HER2 protein stability. Results The mRNA and protein expression levels of CMTM6 in gastric cancer tissue were significantly higher than those in normal paracancerous tissue（P<0.05）. The low expression of CMTM6 significantly inhibited the proliferation，invasion，and migration of AGS and BGC-823 cells and promoted cell apoptosis（P<0.05），while overexpression of CMTM6 significantly promoted the proliferation，invasion，and migration of AGS and BGC-823 cells and inhibited cell apoptosis. Co-IP showed the existence of binding between CMTM6 and HER2，and the low expression of CMTM6 significantly inhibited the expression of HER2 protein（P<0.05） and reduced HER2 protein stability（P<0.05）. Co-transfection of LV-CMTM6 and sh-HER2 in AGS and BGC-823 cells could reverse the effect of CMTM6 overexpression on the proliferation，invasion，migration，and apoptosis of AGS and BGC-823 cells. Conclusion CMTM6 is significantly highly expressed in gastric cancer tissue and cells. CMTM6 can promote HER2 protein stability through targeted binding to HER2，thereby promoting the proliferation，invasion，and migration of gastric cancer cells and inhibiting the apoptosis of gastric cancer cells.