Effect of transmembrane protein 196 on migration and invasion of breast cancer

Zhe ZHANG; Jun FAN; Wenbin LIU; Yan XU

doi:10.16016/j.2097-0927.202112168

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Effect of transmembrane protein 196 on migration and invasion of breast cancer

Clinical Medicine | 更新时间：2026-01-09

- Effect of transmembrane protein 196 on migration and invasion of breast cancer
- Journal of Army Medical University Vol. 44, Issue 14, Pages: 1455-1465(2022)
- 作者机构：
  
  1.400042 重庆，陆军特色医学中心乳腺甲状腺外科
  2.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系：毒理学研究所
  3.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系：军队环境卫生学教研室
- 作者简介：
- 基金信息：
  
  the Clinical Technology Innovation and Cultivation Project of Army Medical University(CX2019LC120)
- DOI：10.16016/j.2097-0927.202112168
  CLC： R394.3;R730.23;R737.9
- Received：20 December 2021，
  
  Revised：2022-03-15，
  
  Published：30 July 2022
- 稿件说明：
移动端阅览
Zhe ZHANG, Jun FAN, Wenbin LIU, et al. Effect of transmembrane protein 196 on migration and invasion of breast cancer[J]. Journal of Army Medical University, 2022, 44(14): 1455-1465.
DOI：

Zhe ZHANG, Jun FAN, Wenbin LIU, et al. Effect of transmembrane protein 196 on migration and invasion of breast cancer[J]. Journal of Army Medical University, 2022, 44(14): 1455-1465. DOI： 10.16016/j.2097-0927.202112168.

摘要

目的

研究跨膜蛋白196(transmembrane protein 196，

TMEM

196)对乳腺癌细胞迁移及侵袭能力的影响。

方法

研究采用癌症基因组图谱(the cancer genome atlas

TCGA)和Oncomine数据库分析

TMEM

196在乳腺癌中的mRNA表达。通过实时定量-聚合酶链反应(quantitative real time-polymerase chain reaction

RT-qPCR)检测

TMEM

196在乳腺癌细胞中的表达，利用Kaplan-Meier数据库分析

TMEM

196对乳腺癌患者预后的影响；采用组织芯片分析

TMEM

196的蛋白水平和预后作用，该队列包含70例癌旁样本和160例浸润性乳腺癌样本，年龄(53.61±13.13)岁，在2001年1月至2004年8月接受手术切除，随访时间2~150个月；通过细胞增殖、划痕愈合和Transwell实验研究

TMEM

196对乳腺癌细胞增殖、迁移及侵袭能力的影响；Western blot检测

TMEM

196对β-连环蛋白(

catenin

)和基质金属蛋白酶7(matrix metalloproteinase 7，

MMP

7)表达的影响。

结果

TMEM

196的mRNA水平和蛋白水平在乳腺癌中均显著降低(

0.05)，在三阴性乳腺癌(triple negative breast cance

r，TNBC)细胞株MDA-MB-231和TNBC组织中最明显(

0.05)，低表达的

TMEM

196和较差的总体生存率(overall survival，OS)有关(

=0.524，95%

: 0.293~0.936，

=0.040)；过表达

TMEM

196之后能够显著抑制乳腺癌细胞的增殖、迁移和侵袭(

0.05)，而干扰

TMEM

196的表达后，能够显著增强细胞的增殖、迁移和侵袭(

0.05)；Western blot提示

TMEM

196能够抑制

catenin

MMP

7信号通路从而降低乳腺癌细胞的运动能力(

0.05)，加入

catenin

抑制剂后能够消除干扰

TMEM

196后所导致的促肿瘤作用(

0.05)。

结论

TMEM

196通过调节

catenin

MMP

7信号通路抑制乳腺癌细胞的迁移和侵袭。

Abstract

Objective

To investigate the effect of transmembrane protein 196 (

TMEM

196) on the migration and invasion of breast cancer cells.

Methods

The Cancer Genome Atlas (TCGA) and Oncomine database were used to analyze the mRNA expression of

TMEM

196 in breast cancer. The expression of

TMEM

196 in breast cancer cells was detected by quantitative real time-polymerase chain reaction (RT-qPCR). Kaplan-Meier database was employed to analyze the effect of

TMEM

196 on the prognosis of breast cancer patients. The protein level and prognostic effect of

TMEM

196 were analyzed by tissue microarray. The cohort included 70 paracancerous samples and 160 invasive breast cancer samples from the patients (53.61±13.13 years old) undergoing surgical resection from January 2001 to August 2004

with a follow-up period of 2 to 150 months. Cell proliferation experiment

scratch healing test and Transwell assay were performed to determine the effect of

TMEM

196 on the proliferation

migration and invasion of breast cancer cells.

Western blot assay was used to explore the regulation of

TMEM

196 on the expression of

catenin

and matrix metalloproteinases 7 (

MMP

7).

Results

The mRNA and protein levels of

TMEM

196 were significantly decreased in breast cancer (

0.05)

and notably

this phenomenon was most obvious in triple negative breast cancer (TNBC) cell line MDA-MB-231 and TNBC tissues (

0.05). Lower expression of

TMEM

196 was associated with poor overall survival (OS) (

=0.524

95%

: 0.293~0.936

=0.040). In addition

overexpression of

TMEM

196 could significantly inhibit the proliferation

migration and invasion of breast cancer cells(

0.05)

while its knockdown can significantly enhances the above abilities(

0.05). The results of Western blot assay indicated that

TMEM

196 inhibited the

catenin

MMP

7 signaling pathway and reduced the motility of breast cancer cells(

0.05). On the contrary

the tumor-promoting effect which caused by knockdown of

TMEM

196 could be eliminated after adding

catenin

inhibitor(

0.05).

Conclusion

TMEM

196 inhibits the migration and invasion of breast cancer cells by regulating the

catenin

MMP

7 signaling pathway.

关键词

Keywords

references

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