YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
誌上シンポジウム
細胞接着分子インテグリンを標的とした新しい抗腫瘍薬の展望
深井 文雄
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ジャーナル フリー

2017 年 137 巻 2 号 p. 137-139

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 The extracellular matrix (ECM) provides a variety of biological signals for cell regulation. It is apparent that some of these signals are derived from functional sites, which are concealed in the higher structure of ECM protein molecules. Previously, we found that fibronectin, a ubiquitous cell adhesive ECM protein, harbors a cryptic functional site termed FNIII14, which can be exposed through the processing of fibronectin by inflammatory proteinases, including matrix metalloproteinase-2 (MMP-2). FNIII14, once exposed, induces a conformational change in beta1-integrins necessary for their functional inactivation, resulting in weakened cell adhesion to the ECM. Interestingly, eukaryotic peptide elongation factor 1A (eEF1A) was recently identified as a membrane receptor mediating this anti-adhesive effect of FNIII14. Here, we show that exposure of FNIII14 from the fibronectin matrix, and its interaction with the membrane receptor eEF1A, contributes to the migration and invasion of cancer cells. Furthermore, an in vivo experiment using a mouse xenograft model shows that FNIII14 could be a promising target for preventing lung metastasis of melanoma.

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© 2017 The Pharmaceutical Society of Japan
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