PT  - JOURNAL ARTICLE
AU  - Min Soo Kim
AU  - Hyun Sook Lee
AU  - Yun Jae Kim
AU  - Sung Gyun Kang
AU  - Do Yup Lee
AU  - Wook Jin
TI  - MEST induces epithelial-mesenchymal transition through IL-6/JAK/STAT3 signaling in breast cancers
AID  - 10.1101/295832
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 295832
4099  - http://biorxiv.org/content/early/2018/04/05/295832.short
4100  - http://biorxiv.org/content/early/2018/04/05/295832.full
AB  - 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 cancer’s 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.