2019 Fiscal Year Annual Research Report
Phosphorylation status of TGF-beta receptor-regulated SMADs in the pathophysiology of triple negative breast cancers
| Project/Area Number |
18K15252
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
裴 恩真 東京医科大学, 医学部, 兼任助教 (40773388)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | Breast cancer / Chemoresistance / TGF-beta / Smad2 / Linker phosphorylation |
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| Outline of Annual Research Achievements |
I have uncovered the novel roles of linker phosphorylation of TGF-β-regulated receptor Smads: Smad2 and Smad3 (pSmad2L and pSmad3L) in chemoresistance of triple-positive breast cancer (TPBC) and epithelial-mesenchymal transition (EMT) of triple negative breast cancer (TNBC). <1> IL-6-induced pSmad2L rendered MCF7 TPBC cells resistant to paclitaxel and tamoxifen. <2> Among MAPKs, which are capable of phosphorylating Smad2 linker regions, JNK is responsible for the chemoresistance of MCF-7 cells. <3> I have identified the target genes and miRNAs of pSmad2L to induce chemoresistance of MCF7 cells by using RNA sequencing of the MCF7 cells transfected with pSmad2L active and inactive mutants compared with the controls. <4> pSmad2L was significantly upregulated in metastatic lesions of Asian breast cancer patient tissue array samples. <5> I have found that pSmad3L induced EMT and chemoresistance of MDA-B-231 TNBC cells.
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