MEST induces Twist-1-mediated EMT through STAT3 activation in breast cancers

被引：67

作者：

Kim, Min Soo ^{[1
]}

Lee, Hyun Sook ^{[2
,3
]}

Kim, Yun Jae ^{[2
,3
]}

Lee, Do Yup ^{[4
]}

Kang, Sung Gyun ^{[2
,3
]}

Jin, Wook ^{[1
]}

机构：

[1] Gachon Univ, Lab Mol Dis & Cell Regulat, Dept Biochem, Sch Med, Incheon 406840, South Korea

[2] Korea Inst Ocean Sci & Technol, Haeyang Ro 385, Busan 49111, South Korea

[3] Univ Sci & Technol, Dept Marine Biotechnol, Daejeon, South Korea

[4] Kookmin Univ, Dept Bio & Fermentat Convergence Technol, BK21 PLUS Program, Seoul 02707, South Korea

来源：

CELL DEATH AND DIFFERENTIATION | 2019年 / 26卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

TO-MESENCHYMAL TRANSITION; EXPRESSION; PEG1/MEST; CELLS; GENE; METASTASIS; GROWTH; PLAYS; INSIGHTS; TWIST;

D O I：

10.1038/s41418-019-0322-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The loss of imprinting of MEST has been linked to certain types of cancer by promoter switching. However, MEST-mediated regulation of tumorigenicity and metastasis are yet to be understood. Herein, we reported that MEST is a key regulator of IL-6/JAK/STAT3/Twist-1 signal pathway-mediated tumor metastasis. Enhanced MEST expression is significantly associated with pathogenesis of breast cancer patients. Also, MEST induces metastatic potential of breast cancer through induction of the EMT-TFs-mediated EMT program. Moreover, MEST leads to Twist-1 induction by STAT3 activation and subsequently enables the induction of activation of the EMT program via the induction of STAT3 nuclear translocation. Furthermore, the c-terminal region of MEST was essential for STAT3 activation via the induction of JAK2/ STAT3 complex formation. Finally, MEST is required for metastasis in an experimental metastasis model. These observations suggest that MEST is a promising target for intervention to prevent tumor metastasis.

引用

页码：2594 / 2606

页数：13

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