Epithelial-to-Mesenchymal Transition and Acquisition of Chemoresistance

2014 Fiscal Year Final Research Report

• Project/Area Number: 24701023
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: University of Toyama
• Principal Investigator: TOGE Masayoshi 富山大学, 大学院医学薬学研究部(医学), 助教 (90456385)
• Co-Investigator(Renkei-kenkyūsha): YOKOYAMA Satoru 富山大学, 和漢医薬学総合研究所・病態生化学分野, 助教 (90613498) ; HAYAKAWA Yoshihiro 富山大学, 和漢医薬学総合研究所・病態生化学分野, 准教授 (10541956) ; SAIKI Ikuo 富山大学, 和漢医薬学総合研究所・病態生化学分野, 教授 (80133776)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 上皮間葉転換 / 抗癌剤耐性

Outline of Final Research Achievements

Non-small-cell Lung cancer (NSCLC) is a common cause of deaths in industrialized countries.Surgery is the most effective therapy for the patients with NSCLC. Recently, cisplatin therapy after surgery is most popular, but it is still controversial that an adjuvant-chemotherapy could give a significant survival advantage in the stage I patients compared with surgery alone.
We focused on TGF-b induced epithelial-to-mesenchymal transition (EMT) because it is involved in both metastasis and chemo-resistance and the mechanism of its EMT-related chemo-resistance has not been known. In this study, we identified MCL1 as a critical molecule for TGF-b induced chemo-resistance in NSCLC cells, A549. Moreover, targeting MCL1 using siRNA or pan-BCL2 inhibitor, obatoclax mesylate, could overcome the TGF-b induced chemoresistance. Collectively, TGF-b induced chemo-resistance and MCL-1 itself could provide a new therapeutic opportunity in NSCLC patients even in post-operative chemotherapies.

Free Research Field

lung cancer