Speaker: Dr. Masanori Nakayama
(Group Leader, Max Planck Institute for Heart and Lung Research, Germany)
(Group Leader, Max Planck Institute for Heart and Lung Research, Germany)
Summary:
Cell proliferation is controlled not only by growth factors, but also by polarization. Disrupted polarity is a hallmark of excessive cell expansion, however a molecular mechanism remains elusive. Polarity protein atypical protein kinase C lambda/iota (aPKCλ), is associated with proliferation and is an oncogene. In endothelia, suppression of aPKCλ impairs proliferation despite hyper-activated vascular endothelial growth factor (VEGF) signaling. In this seminar, I will show the molecular mechanisms to explain this discrepancy. aPKCλ phosphorylates forkhead box O1 (FoxO1) transcription factor, a gatekeeper of endothelial growth. As a result, c-Myc transcription is affected. Importantly, we confirm phosphorylation of FoxO1 by aPKC in more than 70% of the angiosarcoma patients. Our findings may provide a new therapeutic strategy for treatment of malignant cancers, such as angiosarcoma.
Cell proliferation is controlled not only by growth factors, but also by polarization. Disrupted polarity is a hallmark of excessive cell expansion, however a molecular mechanism remains elusive. Polarity protein atypical protein kinase C lambda/iota (aPKCλ), is associated with proliferation and is an oncogene. In endothelia, suppression of aPKCλ impairs proliferation despite hyper-activated vascular endothelial growth factor (VEGF) signaling. In this seminar, I will show the molecular mechanisms to explain this discrepancy. aPKCλ phosphorylates forkhead box O1 (FoxO1) transcription factor, a gatekeeper of endothelial growth. As a result, c-Myc transcription is affected. Importantly, we confirm phosphorylation of FoxO1 by aPKC in more than 70% of the angiosarcoma patients. Our findings may provide a new therapeutic strategy for treatment of malignant cancers, such as angiosarcoma.
Contact:
Yuichiro Nakajima
E-mail:yuichiro.nakajima.d2(at)tohoku.ac.jp