Philadelphia University + Thomas Jefferson University

Wang, Chenguang

< Back



Chenguang Wang, PhD

Contact Dr. Wang

Kimmel Cancer Center
233 S. Tenth Street, Suite 1032
Philadelphia, PA 19107

(215) 503-9341
(215) 923-4498 fax

Expertise & Research Interests

My laboratory focuses on understanding the mechanisms utilized by steroid nuclear receptors in regulation of glucose metabolism, cellular proliferation and cancer progression. Our research is directed towards the overall comprehension of the steroid nuclear receptor signaling and its role in lipogenesis and tumorigenesis.

The steroid receptor family of nuclear receptors is a large class of ligand-dependent transcription factors involved in a wide array of cellular processes, including proliferation, differentiation, and homeostasis. Alterations of nuclear receptor signaling have been linked to human diseases, including variety of cancers. Upon ligand binding, nuclear receptors undergo a dramatic conformational change, inducing a release of corepressors and subsequent recruitment of different coactivators. This results in transcriptional activation via mechanisms that include histone acetylation and chromatin remodeling. Function of nuclear receptors is also regulated by post-translational modification including phosphorylation, acetylation, and sumoylation. In our lab we have demonstrated that estrogen receptor and androgen receptor are acetylated by histone acetyltransferases, and current research is focusing on elucidating the role of acetylation of nuclear receptors (estrogen receptor, androgen receptor, and PPARgamma) in cellular proliferation/differentiation and their potential role in cancer initiation and progression.

Our previous results indicate that cyclin D1, at transcriptional level, is down regulated by activation of PPARgamma. Likewise, PPARgamma function can be antagonized by activated cyclin D1. A growing body of evidence suggests that cyclin D1 promotes cell survival and that PPARgamma induces cell death through non-apoptotic pathway. Our data shows that activation of PPARgamma induces HIF-1 and Bnip3 expression. Moreover, Bnip3 expression was found to be increased in cyclin D1-deficient cells, which is consistent with the reciprocal regulation between cyclin D1 and PPARgamma. Upregulation of Bnip3 was reported to correlate with the induction of autophagy, which, particularly under hypoxic condition (solid tumor), directly affects a number of malignant phenotypes, including programmed cell death (apoptosis and non-apoptotic cell death), therapeutic resistance, angiogenesis, tumor invasion and metastasis. These hypoxia-associated phenotypes are mainly controlled by specific hypoxia-induced transcription factors, including HIF-1a. We are currently investigating whether PPARgamma and cyclin D1 cooperate in regulation of gene expression and autophagic cell death in tumors induced by stimuli (such as hormones) and/or hypoxic microenvironments.

Our most recent work identified PPARgamma is acetylated in cells at nice distinct lysine residues. Acetylation of PPARgamma enhances tumor growth and lipid synthesis via an acetylated K154/155. Deacetylation of PPARgamma at K154 is mediated by SIRT1. The PPARgamma site determines the induction of lipogenesis and breast tumor growth in mice. Loss of SIRT1 function and gain-of-function of PPARgamma converge on common gene signaling pathways in vivo. The PPARgamma acetylation signature is increased in human breast cancer, associated with a relative loss of SIRT1 correlating with poor patient outcome. Tumor growth consequent upon the loss of tumor suppressors or activation of oncogenic growth signals is known to drive tumor metabolism and the synthesis of intracellular nutrients and lipids, the building blockers for the newly divided cells. The collaborative oncogenic function of PPARgamma correlated with the capacity to induce lipid, without the induction of cell-cycle control gene expression, or induction of the mitogenic signaling Akt and MAP kinases. The induction of anabolic metabolism by PPARgamma acetylation and the consequent induction of tumor growth are consistent with an evolving model in which metabolic reprogramming to support anabolic growth is considered a hallmark of cancer.


Publications for this author are currently unavailable.