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

Abstract

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.

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Acknowledgements

This work was supported by a National Research Foundation of Korea grant (NRF-2012R1A2A2A01002728 to WJ and 2015R1D1A1A01059406, 2018R1C1B6008372 to MSK). This work was supported by the Cooperative Research Program for Agriculture Science & Technology Development (Project no. PJ0132772019 to WJ), Rural Development Administration. This research was a part of the project entitled ‘Development of Biomedical materials based on marine proteins’, funded by the Ministry of Oceans and Fisheries, Korea.

Author information

MSK, SKK, and WJ designed research; MSK, HSL, YJK, and DYL performed research; MSK, SKK, and WJ analyzed data; and SKK and WJ wrote the main manuscript text.

Correspondence to Sung Gyun Kang or Wook Jin.

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