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bioRxiv · 10.1101/295832

MEST induces epithelial-mesenchymal transition through IL-6/JAK/STAT3 signaling in breast cancers

Kim, M.·Lee, H. S.·Kim, Y. J.·Kang, S. G.·Lee, D. Y.·Jin, W.
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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 significantly increases the breast cancers ability to metastasize from the mammary gland to the lung. These observations suggest that MEST is a promising target for intervention to prevent tumor metastasis.

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Kim, M., Lee, H. S., Kim, Y. J., Kang, S. G., Lee, D. Y., Jin, W.. 2018-04-05. MEST induces epithelial-mesenchymal transition through IL-6/JAK/STAT3 signaling in breast cancers. https://doi.org/10.1101/295832

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