Cited 91 times in
Induction of metastatic potential by TrkB via activation of IL6/JAK2/STAT3 and PI3K/AKT signaling in breast cancer
DC Field | Value | Language |
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dc.contributor.author | 정준 | - |
dc.date.accessioned | 2018-03-26T16:56:41Z | - |
dc.date.available | 2018-03-26T16:56:41Z | - |
dc.date.issued | 2015 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/156986 | - |
dc.description.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. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Impact Journals | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Blotting, Western | - |
dc.subject.MESH | Breast Neoplasms/genetics | - |
dc.subject.MESH | Breast Neoplasms/metabolism* | - |
dc.subject.MESH | Breast Neoplasms/therapy | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Dogs | - |
dc.subject.MESH | Gene Expression Regulation, Neoplastic/drug effects | - |
dc.subject.MESH | HEK293 Cells | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Interleukin-6/genetics | - |
dc.subject.MESH | Interleukin-6/metabolism* | - |
dc.subject.MESH | Interleukin-6/pharmacology | - |
dc.subject.MESH | Janus Kinase 2/genetics | - |
dc.subject.MESH | Janus Kinase 2/metabolism* | - |
dc.subject.MESH | Madin Darby Canine Kidney Cells | - |
dc.subject.MESH | Membrane Glycoproteins/genetics | - |
dc.subject.MESH | Membrane Glycoproteins/metabolism* | - |
dc.subject.MESH | Mice, Inbred BALB C | - |
dc.subject.MESH | Mice, Nude | - |
dc.subject.MESH | Neoplasm Metastasis | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/genetics | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/metabolism* | - |
dc.subject.MESH | Protein-Tyrosine Kinases/genetics | - |
dc.subject.MESH | Protein-Tyrosine Kinases/metabolism* | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt/genetics | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt/metabolism* | - |
dc.subject.MESH | RNA Interference | - |
dc.subject.MESH | RNAi Therapeutics/methods | - |
dc.subject.MESH | Receptor, trkB | - |
dc.subject.MESH | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject.MESH | STAT3 Transcription Factor/genetics | - |
dc.subject.MESH | STAT3 Transcription Factor/metabolism* | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Signal Transduction/genetics | - |
dc.subject.MESH | Twist-Related Protein 1/genetics | - |
dc.subject.MESH | Twist-Related Protein 1/metabolism | - |
dc.subject.MESH | Xenograft Model Antitumor Assays/methods | - |
dc.title | Induction of metastatic potential by TrkB via activation of IL6/JAK2/STAT3 and PI3K/AKT signaling in breast cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Surgery | - |
dc.contributor.googleauthor | Min Soo Kim l Won Sung Lee | - |
dc.contributor.googleauthor | Joon Jeong | - |
dc.contributor.googleauthor | Seong-Jin Kim | - |
dc.contributor.googleauthor | Wook Jin | - |
dc.identifier.doi | 10.18632/oncotarget.5522 | - |
dc.contributor.localId | A03727 | - |
dc.relation.journalcode | J02421 | - |
dc.identifier.eissn | 1949-2553 | - |
dc.identifier.pmid | 26515594 | - |
dc.subject.keyword | IL-6/JAK2/STAT3 pathway | - |
dc.subject.keyword | PI3K/AKT pathway | - |
dc.subject.keyword | TrkB | - |
dc.subject.keyword | epithelial-mesenchymal transition (EMT) | - |
dc.subject.keyword | metastasis and tumorigenicity | - |
dc.contributor.alternativeName | Jeong, Joon | - |
dc.contributor.affiliatedAuthor | Jeong, Joon | - |
dc.citation.volume | 6 | - |
dc.citation.number | 37 | - |
dc.citation.startPage | 40158 | - |
dc.citation.endPage | 40171 | - |
dc.identifier.bibliographicCitation | ONCOTARGET , Vol.6(37) : 40158-40171, 2015 | - |
dc.identifier.rimsid | 41295 | - |
dc.type.rims | ART | - |
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