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Objective To investigate the effect of transmembrane protein 196 (TMEM196) 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 TMEM196 in breast cancer. The expression of TMEM196 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 TMEM196 on the prognosis of breast cancer patients. The protein level and prognostic effect of TMEM196 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 TMEM196 on the proliferation, migration and invasion of breast cancer cells. Western blot assay was used to explore the regulation of TMEM196 on the expression of β-catenin and matrix metalloproteinases 7 (MMP7). Results The mRNA and protein levels of TMEM196 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 TMEM196 was associated with poor overall survival (OS) (HR=0.524, 95%CI: 0.293~0.936, P=0.040). In addition, overexpression of TMEM196 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 TMEM196 inhibited the β-catenin/MMP7 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 TMEM196 could be eliminated after adding β-catenin inhibitor(P < 0.05). Conclusion TMEM196 inhibits the migration and invasion of breast cancer cells by regulating the β-catenin/MMP7 signaling pathway.