| Co-Investigator(Kenkyū-buntansha) |
YOKOTA Eriko Kyoritsu College of Pharmacy, Pharmaceutical Dept, Assistant, 薬学部, 助手 (10222457)
SONODA Yoshiko Kyoritsu College of Pharmacy, Pharmaceutical Dept, Ass. Prof., 薬学部, 助教授 (30050743)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Focal adhesion kinase (FAK) is a tyrosine kinase expressed in many type of cells, especially in cancer cells such as invasive or metastatic colon carcinomas, breast tumors, oral cancers. FAK plays an important role in cell growth, survival, and migration, thus rendering a critical role in development of tumor cells. FAK is tyrosine-phosphorylated and activated by many types of stimuli, such as bombesin, bradykinin, platelet-derived growth factor, hepatocyte growth factor, insulin, chemokines. We found that FAK is tyrosine-phosphorylated by reactive oxygen species and the tyrosine-phosphorylation was prerequisite for the antiapoptotic function of FAK. In addition, PKB/Akt pathway has been implicated in the survival signal of FAK. We identified that FAK overexpression leads to constitutive activation of survival pathwayand anti-apoptotic role in the apoptosis induced by oxidative stress, anti-cancer drug, irradiation in anchorage-independent cells, IIL-60. Other some protein tyrosine kinase overexpression and/or deregulation also lead to constitutive downstream kinase activation, infinite proliferation and oncogenic transformation. We assumed that FAK may be like an oncogene and become potential targets by anti-cancer strategies, particularly emphasizing the role of FAK linking to survival pathway.
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