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Study on a membrane receptor mediating de-adhesive effect of the cryptic site FNIII14 within fibronectin molecule and its pathophysiological roles

板垣 圭祐 Keisuke Itagaki 東京理科大学 DOI:info:doi/10.20604/00003643

2021.06.09

概要

固形組織を構成する細胞の増殖、分化、生/死などの機能発現は、接着分子インテグリンを介した細胞外マトリックス(E C M ) への接着により調節されている。接着性の細胞は足場であるECMへの接着を喪失すると細胞死が誘導され、これを足場依存性の細胞死アノイキスと呼ぶ。機能性E C M タンパクであるフィブロネクチン(F N ) 分子内にはp l インテグリンを不活性化する機能部位FN1II14が存在し、この部位がマトリックスメタロプロテアーゼ(MMP)などのECM分解酵素による限定分解を介して表出することが報告されている。この機能配列を含むFNIII14ペプチドはp l インテグリンの活性化を阻害することで様々な細胞機能に影響を及ぼすことが報告されている。

本研究ではまず、FNIII14の反接着作用を媒介する受容体として同定された細胞質タンパクであるタンパク質翻訳伸長因子eukaryotic elongation factor1A (eEFlA)が細胞膜上にも存在し、アノイキスを誘導することを示す(第1項)。次に、FNIII14と細胞膜上のeEFlAの相互作用によって引き起こされる反接着作用が病態生理学的にどのような役割を果たすのか、がん細胞の移動及び浸潤に着目して解析する(第2項)。

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