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跨膜蛋白196对乳腺癌迁移及侵袭能力的影响
Effect of transmembrane protein 196 on migration and invasion of breast cancer
- 陆军军医大学学报 2022年44卷第14期 页码：1455-1465
- 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：
[徐琰，E-mail：xy931@163.comXU Yan, E-mail: xy931@163.com
- 基金信息：陆军军医大学临床技术创新与培养项目(CX2019LC120)
DOI：10.16016/j.2097-0927.202112168
中图分类号： R394.3;R730.23;R737.9收稿：2021-12-20，
修回：2022-03-15，
纸质出版：2022-07-30
- 稿件说明：
移动端阅览
张哲, 樊俊, 刘文斌, 等. 跨膜蛋白196对乳腺癌迁移及侵袭能力的影响[J]. 陆军军医大学学报, 2022,44(14):1455-1465.
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.
张哲, 樊俊, 刘文斌, 等. 跨膜蛋白196对乳腺癌迁移及侵袭能力的影响[J]. 陆军军医大学学报, 2022,44(14):1455-1465. DOI： 10.16016/j.2097-0927.202112168.
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
2
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
2
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(
β
-
catenin
)和基质金属蛋白酶7(matrix metalloproteinase 7，
MMP
7)表达的影响。
结果
2
TMEM
196的mRNA水平和蛋白水平在乳腺癌中均显著降低(
P
<
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(
P
<
0.05)，低表达的
TMEM
196和较差的总体生存率(overall survival，OS)有关(
HR
=0.524，95%
CI
: 0.293~0.936，
P
=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(
P
<
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(
P
<
0.05)；Western blot提示
TMEM
196能够抑制
β
-
catenin
/
MMP
7信号通路从而降低乳腺癌细胞的运动能力(
P
<
0.05)，加入
β
-
catenin
抑制剂后能够消除干扰
TMEM
196后所导致的促肿瘤作用(
P
<
0.05)。
结论
2
TMEM
196通过调节
β
-
catenin
/
MMP
7信号通路抑制乳腺癌细胞的迁移和侵袭。
Abstract
Objective
2
To investigate the effect of transmembrane protein 196 (
TMEM
196) on the migration and invasion of breast cancer cells.
Methods
2
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
β
-
catenin
and matrix metalloproteinases 7 (
MMP
7).
Results
2
The mRNA and protein levels of
TMEM
196 were significantly decreased in breast cancer (
P
<
0.05)
and notably
this phenomenon was most obvious in triple negative breast cancer (TNBC) cell line MDA-MB-231 and TNBC tissues (
P
<
0.05). Lower expression of
TMEM
196 was associated with poor overall survival (OS) (
HR
=0.524
95%
CI
: 0.293~0.936
P
=0.040). In addition
overexpression of
TMEM
196 could significantly inhibit the proliferation
migration and invasion of breast cancer cells(
P
<
0.05)
while its knockdown can significantly enhances the above abilities(
P
<
0.05). The results of Western blot assay indicated that
TMEM
196 inhibited the
β
-
catenin
/
MMP
7 signaling pathway and reduced the motility of breast cancer cells(
P
<
0.05). On the contrary
the tumor-promoting effect which caused by knockdown of
TMEM
196 could be eliminated after adding
β
-
catenin
inhibitor(
P
<
0.05).
Conclusion
2
TMEM
196 inhibits the migration and invasion of breast cancer cells by regulating the
β
-
catenin
/
MMP
7 signaling pathway.
关键词
Keywords
references
BRAY F, FERLAY J, SOERJOMATARAM I, et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.
SIEGEL R L, MILLER K D, FUCHS H E, et al . Cancer statistics, 2021[J ] . CA Cancer J Clin, 2021, 71(1): 7-33. DOI: 10.3322/caac.21654.
MEI J, HAO L Y, LIU X R, et al . Comprehensive analysis of peroxiredoxins expression profiles and prognostic values in breast cancer[J ] . Biomark Res, 2019, 7: 16. DOI: 10.1186/s40364-019-0168-9.
WU S J, GUO X Y, ZHOU J J, et al . High expression of UNC5B enhances tumor proliferation, increases metastasis, and worsens prognosis in breast cancer[J ] . Aging, 2020, 12(17): 17079-17098. DOI: 10.18632/aging.103639.
NEUPERGER P, BALOG J Á, TISZLAVICZ L, et al . Analy-sis of the single-cell heterogeneity of adenocarcinoma cell lines and the investigation of intratumor heterogeneity reveals the expression of transmembrane protein 45A (TMEM45A) in lung adenocarcinoma cancer patients[J ] . Cancers, 2021, 14(1): 144. DOI: 10.3390/cancers14010144.
WU J W, TANG X H, YU X J, et al . TMEM60 promotes the proliferation and migration and inhibits the apoptosis of glioma through modulating AKT signaling[J ] . J Oncol, 2022, 2022: 9913700. DOI: 10.1155/2022/9913700.
KANG C F, ROSTOKER R, BEN-SHUMEL S, et al . TMEM176B regulates AKT/mTOR signaling and tumor growth in triple-negative breast cancer[J ] . Cells, 2021, 10(12): 3430. DOI: 10.33 90/cells10123430.
LIU W B, HAN F, HUANG Y S, et al . TMEM196 hyper-methylation as a novel diagnostic and prognostic biomarker for lung cancer[J ] . Mol Carcinog, 2019, 58(4): 474-487. DOI: 10.1002/mc.22942.
LIU W B, HAN F, JIANG X, et al . TMEM196 acts as a novel functional tumour suppressor inactivated by DNA methylation and is a potential prognostic biomarker in lung cancer[J ] . Oncotarget, 2015, 6(25): 21225-21239. DOI: 10.18632/oncotarget.4237.
但德苗, 郭忠建. 蛋白质核质转运的过程和应用[J]. 中国细胞生物学学报, 2021, 43(9): 1891-1900.
DAN D M, GUO Z J. The process and application of nucleocytoplasmic transport of proteins[J]. Chin J Cell Biol, 2021, 43(9): 1891-1900.
CASSANDRI M, BUTERA A, AMELIO I, et al . ZNF750 represses breast cancer invasion via epigenetic control of prometastatic genes[J ] . Oncogene, 2020, 39(22): 4331-4343. DOI: 10.1038/s41388-020-1277-5.
MARX S, DAL MASO T, CHEN J W, et al . Transmembrane (TMEM) protein family members: poorly characterized even if essential for the metastatic process[J ] . Semin Cancer Biol, 2020, 60: 96-106. DOI: 10.1016/j.semcancer.2019.08.018.
HURT B, SCHULICK R, EDIL B, et al . Cancer-promoting mechanisms of tumor-associated neutrophils[J ] . Am J Surg, 2017, 214(5): 938-944. DOI: 10.1016/j.amjsurg.2017.08.003.
SHARMA R, SHARMA R, KHAKET T P, et al . Breast cancer metastasis: putative therapeutic role of vascular cell adhesion molecule-1[J ] . Cell Oncol (Dordr), 2017, 40(3): 199-208. DOI: 10.1007/s13402-017-0324-x.
JIANG H M, CHEN H B, WAN P, et al . Upregulation of TMEM45A promoted the progression of clear cell renal cell carcinoma in vitro[J ] . J Inflamm Res, 2021, 14: 6421-6430. DOI: 10.2147/JIR.S341596.
JIANG X Y, WANG L, LIU Z Y, et al . TMEM48 promotes cell proliferation and invasion in cervical cancer via activation of the Wnt/β-catenin pathway[J ] . J Recept Signal Transduct Res, 2021, 41(4): 371-377. DOI: 10.1080/10799893.2020.1813761.
AO X D, LI X X, CHENY X, et al . TMEM98 mRNA promotes proliferation and invasion of gastric cells by directly interacting with NF90 protein[J ] . Cell Biol Int, 2020, 44(9): 1820-1 830. DOI: 10.1002/cbin.11375.
PAREJA F, JEYER F C, MARCHIO C, et al . Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants[J ] . NPJ Breast Cancer, 2016, 2: 16036. DOI: 10.1038/npjbcancer.2016.36.
ZHENG K, YAO S, YAO W, et al . Association between RSK 2 and clinical indexes of primary breast cancer: a meta-analysis based on mRNA microarray data[J ] . Front Genet, 2021, 12: 770134. DOI: 10.3389/fgene.2021.770134..
CHEN Y, LI X, XU J, et al . Knockdown of nuclear receptor binding SET domain-containing protein 1 (NSD1) inhibits proliferation and facilitates apoptosis in paclitaxel-resistant breast cancer cells via inactivating the Wnt/β-catenin signaling pathway[J ] . Bioengineered, 2022, 13(2): 3526-3536. DOI: 10.1080/21655979.2021.2018973.
PHAM S H, PRATT K, OKOLICSANYI R K, et al . Syndecan-1 and-4 influence Wnt signaling and cell migration in human breast cancers[J ] . Biochimie, 2022: 2022Feb17;S0300-2022Feb17;S9084(22)00024-4. DOI: 10.1016/j.biochi.2022.01.014.
ZHANG W, RUAN X H, LI Y S, et al . KDM1A promotes thyroid cancer progression and maintains stemness through the Wnt/β-catenin signaling pathway[J ] . Theranostics, 2022, 12(4): 1500-1517. DOI: 10.7150/thno.66142.
LIU L D, WANG L F, LI X J, et al . The roles of HOXB8through activating Wnt/β-catenin and STAT3 signaling pathways in the growth, migration and invasion of ovarian cancer cells[J ] . Cytotechnology, 2022, 74(1): 77-87. DOI: 10.1007/s10616-021-00508-w.
HAN B C, ZHOU B, QU Y, et al . FOXC1-induced non-canonical WNT5A-MMP7 signaling regulates invasiveness in triple-negative breast cancer[J ] . Oncogene, 2018, 37(10): 1399-1408. DOI: 10.1038/s41388-017-0021-2.
NADANAKA S, KINOUCHI H, KITAGAWA H. Chondroitin sulfate-mediated N-cadherin/β-catenin signaling is associated with basal-like breast cancer cell invasion[J]. J Biol Chem, 2018, 293(2): 444-465. DOI: 10.1074/jbc.M117.814509.
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