Secreting protein p53PAD7 suppresses tumor proliferation via the Hippo signaling pathway

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16789
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tokyo University of Science (2020-2021); National Cancer Center Japan (2019)
• Principal Investigator: Takikawa Masahiro 東京理科大学, 理工学部応用生物科学科, 助教 (80807834)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: がん抑制遺伝子 / Hippoシグナル経路 / アポトーシス / p53

Outline of Final Research Achievements

p53PAD7 is one of a target gene of p53. Overexpression of p53PAD7 leads to inhibition of cell proliferation but the molecular mechanisms were still unknown. We found that p53PAD7 is secreted out of the cellular membrane and that addition of recombinant p53PAD7 protein to culture media leads to inhibition of cell proliferation. Mass spectrometric analysis identified that receptor candidates includes protocadherin families that is related to Hippo signaling pathway. In this study, we analyzed changes in mRNA expression profiles in cells treated with recombinant p53PAD7. Furthermore, we investigated the effect of p53PAD7 to tumor progression in mice.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

胃がんと乳がんの一部ではp53PAD7のプロモーター領域が高度にメチル化されることで発現が抑制されることが明らかになっており、p53PAD7の発現低下は予後不良マーカーと考えられている。リコンビナントp53PAD7タンパク質を添加した細胞のmRNA発現量を網羅的に解析した結果、アポトーシスを起こした細胞に見られる発現変化が観察された。p53の下流遺伝子であるp53PAD7を介して、癌化した細胞の周辺にアポトーシスを起こし、排除させるための機構として働いていると考えられる。