Biography | |
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Prof. Changhua Wang Wuhan University School of Basic Medical Sciences, China |
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Title: Cancer-derived exosomes modulate energy metabolism of skeletal muscle cells and adipocytes | |
Abstract:
Accumulating evidences have demonstrated the closely association between diabetes and cancers including breast cancer. The impaired glucose and lipid metabolism in the patients with diabetes facilitatescarcinogenesis,progression,and metastasis of some kinds of cancers. On the other hand, advanced cancer leads to aberrant energy metabolism. Cancer cachexia is a wasting disordercharacterized by losses of skeletal muscle and adipose tissue, whichaccompany metabolic changes. However, the underlying mechanisms remain poorly understood.We found that tumor-surrounding adipocytes exhibit an altered phenotype in terms of up-regulated beige/brown characteristics and increased catabolism associated with an activated state characterized by the release of metabolites, including free fatty acids, pyruvate, lactate and ketone bodies.Using the models of co-culture systems, we confirmed thatbreast cancer-derived exosomes increased catabolism and released the metabolites in adipocytes and skeletal muscle cells, through inhibiting PPARγ signaling by cancer cell-secreted miR-155.In addition, induction of beige/brown differentiation and remodeling metabolism in resident adipocyteswere attributed tocancer-derived exosomes containing high levels of miRNA-144 and miRNA-126. miRNA-144 promoted beige/brown adipocyte characteristics by down-regulating the MAP3K8/ERK1/2/PPARγ axis, and exosomal miRNA-126 remodeled metabolism by disrupting IRS/Glut-4 signaling, activating the AMPK/autophagy pathway and stabilizing HIF1α expression in imminent adipocytes.These results clearly indicated thatexosomalmiRNAs from cancer cells reprogram systemic energy metabolism to promote cancer cachexia.
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Biography: Education: Sept. 1998 – Jun. 2001 Wuhan University School of Medicine, Ph.D Sept. 1988 – Jun. 1991 Hubei Medical University, M.S Sept. 1983 – Jun. 1988 Hubei Medical University, M.D Work Experiences: Dec. 2009 – present: Professor Department of Pathophysiology, Wuhan University School of Basic Medical Sciences Sept. 2008 – Nov. 2009: Associate Professor Department of Pathophysiology, Wuhan University School of Basic Medical Sciences Jul. 2001 – Aug. 2008: Associate Professor Department of Physiology, Wuhan University School of Basic Medical Sciences Jan. 1993 – Aug. 1998: Associate Professor Department of Physiology, Yangtze University School of Medicine Jul. 1991 – Dec. 1992: Physician in charge Department of Cardiovascular Medicine, The 1st Hospital of Jingzhou City Work Experiences-Overseas: Jan. 2014 – Aug. 2015 Assistant Professor Research The University of South Dakota Sanford Medical College, United States Oct. 2010 – Sept. 2011 Visiting Research Scientist The University of South Dakota Sanford Medical College, United States Jul. 2004 – Sept. 2008 Research Scientist University of Texas Health Science Center at San Antonio,United States Apr. 2003 – Aug. 2003 Senior Visiting Scholar Henri Poincare Université, Nancy 1, France Research Interests: My research interest focuses on the molecular mechanism of insulin resistance, adiponectin signaling pathway, and the connection between type 2 diabetes and breast cancer and liver cancer. Grants: 1. Title: PKCdelta-mediated unfolded protein response and insulin resistance. PI: Changhua Wang Natural Science Foundation of China (30971155/ H0712) 2. Title: APPL1-mediated inhibitory effects of adiponectin on hepatic gluconeogenesis. PI: Changhua Wang Natural Science Foundation of China (81170790/ H0718) 3. Title: The role of DNER in the inhibitory impacts of insulin signaling no hepatic gluconeogenesis. PI: Changhua Wang Natural Science Foundation of China (81870550/ H0712) |