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

Cell Death and Differentiation, ISSN: 1476-5403, Vol: 26, Issue: 12, Page: 2594-2606
2019
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Article Description

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.

Bibliographic Details

Kim, Min Soo; Lee, Hyun Sook; Kim, Yun Jae; Lee, Do Yup; Kang, Sung Gyun; Jin, Wook

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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