Investigation of abnormal cytokine signaling and the development of the drugs modulating these signaling

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(1) We previously reported that a FAKY929F mutant in the B16F10 melanoma cell line gave poor metastasis. Here, we identified that the phospholipid protein(PLP) 2 was downregulated in this cell line, acting as an effector molecule downstream of FAK. Why PLP2 induces the metastatic activity was investigated in vitro and in vivo.(2) A JAK2 mutant, JAK2V617F was constitutively active and induced abnormal proliferation, tumorigenesis in nude mice, as well as exhibited resistance to antitumor drugs including cisplatin. The reason why JAK2V617F has such potent activities was studied. We presented a notion that JAK2 mutation constitutively activated STAT5, which enhanced various transcription factors and kinases including c-Myc, Aurora kinaseA or Pim-1/2, thus inducing transformation in vitro and in vivo.