Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis

• DOI: 10.1016/j.celrep.2014.10.039
• Publication Date: 2014-11-17T01:32:43Z
• Authors: Anindya Chatterjee; Joydeep Ghosh; Baskar Ramdas; Raghuveer Singh Mali; Holly Martin; Michihiro Kobayashi; Sasidhar Vemula; Victor H. Canela; Emily R. Waskow; Valeria Visconte; Ramon V. Tiu; Catherine C. Smith; Neil Shah; Kevin D. Bunting; H. Scott Boswell; Yan Liu; Rebecca J. Chan; Reuben Kapur
• Keywords: STAT5; PAK1

Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients acute myeloid leukemia (AML) myeloproliferative neoplasms (MPNs), currently available drugs largely ineffective. Although Stat5 has been implicated regulating several lymphoid malignancies, how precisely regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream FAK, Rac1 regulated by RacGEF Tiam1, prolongs the mice. Inhibition effector PAK1 mice part inhibiting Stat5. These results reveal a pathway involving FAK/Tiam1/Rac1/PAK1 demonstrate an essential role for these signaling molecules