Molecular mechanisms of tissue formation, regeneration, and tumor suppression by the Ras-ERK pathway antagonist DA-Raf

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04348
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Chiba University
• Principal Investigator: ENDO Takeshi 千葉大学, 大学院理学研究院, 教授 (30194038)
• Co-Investigator(Renkei-kenkyūsha): TAKANO Kazunori 千葉大学, 大学院理学研究院, 助教 (60466860)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Ras-ERK経路 / 肺胞形成 / 筋細胞分化 / 筋再生 / がん抑制 / 分子機構

Outline of Final Research Achievements

This research project aimed to elucidate signaling and molecular mechanisms of (1) lung alveolarization, (2) skeletal muscle cell differentiation and regeneration, and (3) tumor suppression by the Ras-ERK pathway antagonist DA-Raf. We found that (1) suppression of the Ras-ERK pathway by DA-Raf is essential for TGF-β1-induced epithelial-mesenchymal transition from alveolar epithelial type 2 cells to myofibroblasts. (2) Suppression of the Ras-ERK pathway by DA-Raf is required for the induction of skeletal myocyte differentiation and apoptosis during myocyte differentiation. (3) The expression of DA-Raf was lost in tumor cells with constitutively active KRAS mutations. Inactivating mutations and SNP of DA-Raf did not suppress active K-Ras mutant-induced tumor phenotypes. Thus, DA-Raf represents a tumor suppressor protein against K-Ras-induced tumorigenesis.

Free Research Field

分子細胞生物学