Elucidation of molecular mechanisms underlying development and progression of rare cancers caused by alteration of transcriptional regulation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kumamoto University
• Principal Investigator: Kadomatsu Tsuyoshi 熊本大学, 大学院生命科学研究部(医), 助教 (90555757)
• Co-Investigator(Renkei-kenkyūsha): ENDO Motoyoshi 熊本大学, 大学院生命科学研究部, 助教 (40398243) ; BABA Masaya 熊本大学, 国際先端医学研究機構, 准教授 (10347304)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 稀少がん / 転写制御 / がん微小環境

Outline of Final Research Achievements

In this study, we investigated the molecular mechanisms underlying development and progression of rare cancers from the point of view of alteration of transcriptional regulatory mechanisms. We found that TFE3 fusion gene, which is a causative gene for Xp11.2 translocation renal cell carcinoma, increases the ANGPTL2 expression and that TFE3 fusion gene-mediated ANGPTL2 induction could be implicated in development and progression of Xp11.2 translocation renal cell carcinoma. In addition, we showed that changes in tumor microenvironments in the primary tumor tissue increase the IL-6 expression in osteosarcoma cells through TET2-mediated DNA demethylation and that IL-6 signaling accelerates lung metastasis by enhancing the expression of an adhesion molecule and metabolic reprograming in osteosarcoma cells. Moreover, our current results suggested that inhibition of IL-6 signaling in osteosarcoma cells could be a novel therapeutic approach for lung metastasis in osteosarcoma.

Free Research Field

分子遺伝学