Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway.
CMTM3 (CKLF-like MARVEL transmembrane domain containing 3) possesses tumor suppressor properties in multiple types of malignancies. Restoration of CMTM3 significantly inhibits the metastasis of gastric cancer, and its expression level is correlated with prognosis. However, the physiological effects and the mechanism of CMTM3 remain unknown. Here, we suppress CMTM3 expression by shRNA to explore its endogenous effects and its mechanism of action in gastric cancer. Stable knockdown of CMTM3 promotes cell migration, invasion and tumor metastasis, increases MMP2 expression and enhances MMP2 activity. CMTM3 inhibits EMT along with the upregulation of E-cadherin and the downregulation of N-cadherin, Vimentin and Twist1. It has no obvious effects on Zeb1 and Snail. CMTM3 suppresses the phosphorylation of STAT3 but not Akt. More importantly, the EMT phenotype and cell migration induced by CMTM3 knockdown can be reversed by the Jak2/STAT3 inhibitor JSI-124 or by siRNA against STAT3 or Twist1. Overall, this study demonstrates that knockdown of CMTM3 promotes the metastasis of gastric cancer through the STAT3/Twist1/EMT pathway.
['Yuan|Wanqiong|W|', 'Li|Ting|T|', 'Mo|Xiaoning|X|', 'Wang|Xiaolin|X|', 'Liu|Baocai|B|', 'Wang|Wenyan|W|', 'Su|Yu|Y|', 'Xu|Lan|L|', 'Han|Wenling|W|']
D000818:Animals D045744:Cell Line, Tumor D018925:Chemokines D058750:Epithelial-Mesenchymal Transition D015972:Gene Expression Regulation, Neoplastic D055785:Gene Knockdown Techniques D064593:Heterografts D006801:Humans D062792:MARVEL Domain-Containing Proteins D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D009361:Neoplasm Invasiveness D009687:Nuclear Proteins D050796:STAT3 Transcription Factor D015398:Signal Transduction D013274:Stomach Neoplasms D051879:Twist-Related Protein 1
CMTM3 metastasis gastric cancer STAT3 EMT