Elucidation of the mechanism of FAP1-dependent cancer metastasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tsujioka Masatsune 東京医科歯科大学, 難治疾患研究所, プロジェクト講師 (60442985)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん / 接着斑 / FRNK / FAK / FAP1 / DNA損傷ストレス

Outline of Final Research Achievements

I have already demonstrated that FAP1 is involved in cancer progression. In the present study, therefore, I investigated the functions of FAP1 and the regulation of its expression to clarify the FAP1-involved mechanism of cancer progression. Furthermore, I tried to identify candidate chemical compounds to develop anti-cancer drugs targeting to FAP1.
FAP1 proved to be identical to FRNK, a known component of focal adhesions. I found that FRNK was expressed in response to genotoxic stress and strengthened cell-matrix adhesion. I also found that several cancer cells concomitantly expressed FRNK and a genotoxic stress marker in their tissues. Since firm cell attachment is an important element of cancer progression, I propose that cancer progression is facilitated by the FRNK-mediated adhesion of cancer cells continuously exposed to genotoxic stress in their tissues. I identified ML385, which inhibited the expression of FRNK, as a candidate anti-cancer compound.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

FRNKは、その欠損マウスに顕著な欠陥が見られないなど、これまで機能がほとんど分かっていなかった。本研究により、DNA損傷ストレスにおけるFRNKの機能と、それを介した新たな細胞ストレス応答の存在が明らかになった。DNA損傷ストレスは、紫外線や放射線など日常にありふれており、様々な疾患とも関連している。本研究成果が、これらの疾患メカニズムの解明や治療法の確立に繋がることが期待される。特に、がん治療においては、正常組織ではFRNKの機能抑制による影響がほとんど見られないため、副作用の少ない抗がん治療の標的として有望である。