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| Content Provider | PubMed Central |
|---|---|
| Author | Kim, Min Soo Lee, Won Sung Jeong, Joon Kim, Seong-jin Jin, Wook |
| Copyright Year | 2015 |
| Abstract | In metastatic breast cancers, the acquisition of metastatic ability, which leads to clinically incurable disease and poor survival, has been associated with acquisition of epithelial-mesenchymal transition (EMT) program and self-renewing trait (CSCs) via activation of PI3K/AKT and IL6/JAK2/STAT3 signaling pathways. We found that TrkB is a key regulator of PI3K/AKT and JAK/STAT signal pathway-mediated tumor metastasis and EMT program. Here, we demonstrated that TrkB activates AKT by directly binding to c-Src, leading to increased proliferation. Also, TrkB increases Twist-1 and Twist-2 expression through activation of JAK2/STAT3 by inducing c-Src-JAK2 complex formation. Furthermore, TrkB in the absence of c-Src binds directly to JAK2 and inhibits SOCS3-mediated JAK2 degradation, resulting in increased total JAK2 and STAT3 levels, which subsequently leads to JAK2/STAT3 activation and Twist-1 upregulation. Additionally, activation of the JAK2/STAT3 pathway via induction of IL-6 secretion by TrkB enables induction of activation of the EMT program via induction of STAT3 nuclear translocation. These observations suggest that TrkB is a promising target for future intervention strategies to prevent tumor metastasis, EMT program and self-renewing trait in breast cancer. |
| Ending Page | 40171 |
| Starting Page | 40158 |
| File Format | |
| ISSN | 19492553 |
| e-ISSN | 19492553 |
| Journal | Oncotarget |
| Issue Number | 37 |
| Volume Number | 6 |
| Language | English |
| Publisher | Impact Journals LLC |
| Publisher Date | 2015-10-20 |
| Access Restriction | Open |
| Rights Holder | Impact Journals LLC |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
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