Dysregulated JAK2 expression by TrkC promotes metastasis potential, and EMT program of metastatic breast cancer.

ABSTRACT: Metastatic breast cancers are aggressive tumors associated with high levels of epithelial-mesenchymal transition (EMT) markers, activation of IL6/JAK2/STAT3 and PI3K/AKT pathways for cell growth, mobility, invasion, metastasis, and CSC status. We identified a new molecular and functional network present in metastasis that regulates and coordinates with TrkC. Inhibition of SOCS3-mediated JAK2 degradation by TrkC increases total JAK2/STAT3 expression, and then leads to upregulation of Twist-1 through activation of JAK2/STAT3 cascade. Also, TrkC increases secretion and expression of IL-6, suggesting that this autocrine loop generated by TrkC maintains the mesenchymal state by continued activation of the JAK2/STAT3 cascade and upregulation of Twist expression. Moreover, TrkC interacts with the

SUBMITTER: Kim MS 

PROVIDER: S-EPMC5032000 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature