Study of invasion mechanism of cancer cells by proteomic analysis of Rap pathway

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06984
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Takumi Akashi 東京医科歯科大学, 東京医科歯科大学病院, 准教授 (60242202)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 浸潤 / 癌細胞 / プロテオーム / proximity labeling / アクチン / Rap1

Outline of Final Research Achievements

By the proximity-labeling approach, in which the proteins those transiently interact with the bait protein can be specifically biotinylated and purified, actin-related proteins which participate in invasion of cancer cells were investigated in invasive breast cancer cells. With three bait proteins of actin(ACTB), cortactin, and Rap1B, 607 proteins were identified. Among them, 68 proteins remained as the proteins those were overexpressed in the lung adenocarcinomas and correlated to poor prognosis based on open database analysis. Among them, knockdown effect of the 17 genes on in vitro migration of MDA-MB-231 cells were studied by shRNA transduction and 3 proteins remained. Among them, LASP1, an actin-binding protein, was shown to be overexpressed immunohistochemically in lung adenocarcinomas.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

アクチンは細胞運動や細胞外基質の分解を介して癌の浸潤に重要な役割を担う。本研究では一過性に相互作用する分子を同定可能な近年に開発されたproximity labeling法を用いたプロテオーム解析によってアクチンと相互作用し癌の悪性度と相関するこれまでに報告のない候補分子を同定することができた。この成果をもとに癌の浸潤を促進する分子を同定することによって癌の悪性度の評価や浸潤・転移を抑制する創薬対象の発見につながる可能性がある。