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

Zhang Dan; Chen Jing

doi:10.13406/j.cnki.cyxb.003614

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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

Basic research | 更新时间：2025-10-23

- 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
- Journal of Chongqing Medical University Vol. 49, Issue 11, Pages: 1402-1407(2024)
- 作者机构：
  
  1.锦州医科大学附属第一医院导管室，锦州 121000
  2.锦州医科大学附属第一医院日间化疗中心，锦州 121000
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003614
  CLC： R735.2
- Received：25 August 2023，
  
  Revised：2024-01-11，
  
  Accepted：12 March 2024，
  
  Published：28 November 2024
- 稿件说明：
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张丹,陈静.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[J].重庆医科大学学报,2024,49(11):1402-1407.

Zhang Dan,Chen Jing.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[J].Journal of Chongqing Medical University,2024,49(11):1402-1407.
张丹,陈静.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[J].重庆医科大学学报,2024,49(11):1402-1407. DOI： 10.13406/j.cnki.cyxb.003614.

Zhang Dan,Chen Jing.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[J].Journal of Chongqing Medical University,2024,49(11):1402-1407. DOI： 10.13406/j.cnki.cyxb.003614.

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（

0.05）. The low expression of CMTM6 significantly inhibited the proliferation，invasion，and migration of AGS and BGC-823 cells and promoted cell apoptosis（

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（

0.05） and reduced HER2 protein stability（

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.

关键词

Keywords

references

Thrift AP ， El-Serag HB . Burden of gastric cancer [J ] . Clin Gastroenterol Hepatol ， 2020 ， 18 （ 3 ）： 534 - 542 ．

Smyth EC ， Nilsson M ， Grabsch HI ， et al . Gastric cancer [J ] . Lancet ， 2020 ， 396 （ 10251 ）： 635 - 648 ．

Tang SY ， Zhou PJ ， Meng Y ， et al . Gastric cancer：an epigenetic view [J ] . World J Gastrointest Oncol ， 2022 ， 14 （ 1 ）： 90 - 109 ．

Wang HF ， Fan Y ， Chen WH ， et al . Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity [J ] . Oncoimmunology ， 2022 ， 11 （ 1 ）： 2011673 ．

Chen L ， Yang QC ， Li YC ， et al . Targeting CMTM6 suppresses stem cell-like properties and enhances antitumor immunity in head and neck squamous cell carcinoma [J ] . Cancer Immunol Res ， 2020 ， 8 （ 2 ）： 179 - 191 ．

Zheng Y ， Wang CD ， Song A ， et al . CMTM6 promotes cell proliferation and invasion in oral squamous cell carcinoma by interacting with NRP1 [J ] . Am J Cancer Res ， 2020 ， 10 （ 6 ）： 1691 - 1709 ．

Guan XD ， Zhang CB ， Zhao JY ， et al . CMTM6 overexpression is associated with molecular and clinical characteristics of malignancy and predicts poor prognosis in gliomas [J ] . EBioMedicine ， 2018 ， 35 ： 233 - 243 ．

Hou XY ， He SS ， Zhang DQ ， et al . Expression and clinical significance of CMTM6 in nonsmall cell lung cancer [J ] . DNA Cell Biol ， 2020 ： 120 - 129 ．

Wang H ， Gao JP ， Zhang RF ， et al . Molecular and immune characteristics for lung adenocarcinoma patients with CMTM6 overexpression [J ] . Int Immunopharmacol ， 2020 ， 83 ： 106478 ．

Xing F ， Gao HL ， Chen GL ， et al . CMTM6 overexpression confers trastuzumab resistance in HER2-positive breast cancer [J ] . Mol Cancer ， 2023 ， 22 （ 1 ）： 6 ．

Zhao D ， Klempner SJ ， Chao J . Progress and challenges in HER2-positive gastroesophageal adenocarcinoma [J ] . J Hematol Oncol ， 2019 ， 12 （ 1 ）： 50 ．

Meric-Bernstam F ， Johnson AM ， Dumbrava EEI ， et al . Advances in HER2-targeted therapy：novel agents and opportunities beyond breast and gastric cancer [J ] . Clin Cancer Res ， 2019 ， 25 （ 7 ）： 2033 - 2041 ．

Zhao YB ， Zhang MH ， Pu HH ， et al . Prognostic implications of pan-cancer CMTM6 expression and its relationship with the immune microenvironment [J ] . Front Oncol ， 2020 ， 10 ： 585961 ．

Zugazagoitia J ， Liu YT ， Toki M ， et al . Quantitative assessment of CMTM6 in the tumor microenvironment and association with response to PD-1 pathway blockade in advanced-stage non-small cell lung cancer [J ] . J Thorac Oncol ， 2019 ， 14 （ 12 ）： 2084 - 2096 ．

Liu LL ， Zhang SW ， Chao X ， et al . Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma [J ] . Cancer Immunol Immunother ， 2021 ， 70 （ 2 ）： 417 - 429 ．

Mezzadra R ， Sun C ， Jae LT ， et al . Identification of CMTM6 and CMTM4 as PD-L1 protein regulators [J ] . Nature ， 2017 ， 549 （ 7670 ）： 106 - 110 ．

Singh K ， Tantravahi U ， Lomme MM ， et al . Updated 2013 College of American Pathologists/American Society of Clinical Oncology（CAP/ASCO） guideline recommendations for human epidermal growth factor receptor 2（HER2） fluorescent in situ hybridization（FISH） testing increase HER2 positive and HER2 equivocal breast cancer cases；retrospective study of HER2 FISH results of 836 invasive breast cancers [J ] . Breast Cancer Res Treat ， 2016 ， 157 （ 3 ）： 405 - 411 ．

Pattanayak B ， Lameirinhas A ， Torres-Ruiz S ， et al . Role of SALL4 in HER2+ breast cancer progression：regulating PI3K/AKT pathway [J ] . Int J Mol Sci ， 2022 ， 23 （ 21 ）： 13292 ．

Kurokawa Y ， Matsuura N ， Kimura Y ， et al . Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer [J ] . Gastric Cancer ， 2015 ， 18 （ 4 ）： 691 - 697 ．

Liang JW ， Zhang JJ ， Zhang T ， et al . Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer：a meta-analysis of the literature [J ] . Tumour Biol ， 2014 ， 35 （ 5 ）： 4849 - 4858 ．

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