Title : MTOR: A Motor of Fibrosis and Metastasis?

Speaker:  Dr. Xiaoqing Gan, Postdoctoral Associate. Department of Pharmacology, School of Medicine, Yale University, USA

Host: Prof. Mingyao Liu

When: 2012-11-6 15:00

Where: Conference Room 534, School of Life Sciences

Abstract：Mammalian target of rapamycin complex (MTORC)2 phosphorylates AGC protein kinases and regulates cellular functions including cell migration. However, its regulation remains poorly understood. Our study explored LPA functions as upstream stimulator of mTORC2, which induces two phases of PKCδ HM phosphorylation. The late phase is mediated by Gα12, which specifically activates ARAF, leading to upregulation of the expression of an E3 ubiquitin ligase RFFL and subsequent ubiquitination and degradation of PRR5L. Destabilization of PRR5L results in PKCδ HM phosphorylation and activation. The further study showed RFFL links the activity of RAF family kinases to mTORC2 signaling in fibroblast migration and tumor cell invasion. Inhibition of mTOR/PKC signaling reduces pulmonary fibrosis in animal model, and impairs metastatic tumor cell mobility. These suggest that the inhibitors of mTOR and PKC may be pharmacological options for fibrosis and metastasis.