Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway.
Knockdown of CMTM3 promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway.
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CMTM3的敲低通过STAT3/Twist1/EMT信号通路促进胃癌转移
DOI：
10.18632/oncotarget.8789
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发表时间：
2016-05-17
期刊：
影响因子：
--
通讯作者：
Han W
中科院分区：
文献类型：
--
作者：
Yuan W;Li T;Mo X;Wang X;Liu B;Wang W;Su Y;Xu L;Han W
CMTM 3（CKLF样MARVEL跨膜结构域包含3）在多种类型的恶性肿瘤中具有肿瘤抑制特性。CMTM 3的恢复显著抑制胃癌的转移，其表达水平与预后相关。然而，CMTM 3的生理作用和机制仍不清楚。在此，我们通过shRNA抑制CMTM 3的表达来探讨其在胃癌中的内源性作用及其作用机制。CMTM 3的稳定敲除促进细胞迁移、侵袭和肿瘤转移，增加MMP 2表达并增强MMP 2活性。CMTM 3沿着E-cadherin的上调和N-cadherin、Vimentin和Twist 1的下调抑制EMT。对Zeb 1和Snail无明显影响。CMTM 3抑制STAT 3的磷酸化，但不抑制Akt。更重要的是，CMTM 3敲低诱导的EMT表型和细胞迁移可以通过Jak 2/STAT 3抑制剂JSI-124或针对STAT 3或Twist 1的siRNA逆转。总之，本研究表明CMTM 3的敲低通过STAT 3/Twist 1/EMT途径促进胃癌的转移。
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.
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影响因子：
4.1
作者：
Han, WL;Lou, YX;Ma, DL
通讯作者：
Ma, DL
影响因子：
11.2
作者：
Pakala SB;Rayala SK;Wang RA;Ohshiro K;Mudvari P;Reddy SD;Zheng Y;Pires R;Casimiro S;Pillai MR;Costa L;Kumar R
通讯作者：
Kumar R
影响因子：
--
作者：
Liu WH;Chen MT;Wang ML;Lee YY;Chiou GY;Chien CS;Huang PI;Chen YW;Huang MC;Chiou SH;Shih YH;Ma HI
通讯作者：
Ma HI
影响因子：
10.5
作者：
Rodriguez-Barrueco R;Yu J;Saucedo-Cuevas LP;Olivan M;Llobet-Navas D;Putcha P;Castro V;Murga-Penas EM;Collazo-Lorduy A;Castillo-Martin M;Alvarez M;Cordon-Cardo C;Kalinsky K;Maurer M;Califano A;Silva JM
通讯作者：
Silva JM
影响因子：
11.5
作者：
Canadas, Israel;Rojo, Federico;Arriola, Edurne
通讯作者：
Arriola, Edurne