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Thomas Jefferson University - Chenguang Wang, Ph.D.
Chenguang Wang, Ph.D.

Cancer Biology
Assistant Professor
Thomas Jefferson University
Jefferson Medical College
Department of Cancer Biology
Kimmel Cancer Center
Mailing Address
233 S. 10th St.
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-9341
Fax: 215-923-4498
Chenguang.Wang@jefferson.edu
Qualifications
Ph.D.
Expertise and Research Interests
My laboratory focuses on understanding the mechanisms utilized by steroid nuclear receptors in regulation of cellular proliferation and progression. Our research is also directed towards the overall comprehension of the steroid nuclear receptor signaling and its role in tumorigenesis and differentiation.
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 PPARg) 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 PPARg. Likewise, PPARg function can be antagonized by activated cyclin D1. A growing body of evidence suggests that cyclin D1 promotes cell survival and that PPARg induces cell death through non-apoptotic pathway. Our data shows that activation of PPARg 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 PPARg. 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 PPARg 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.
Keywords
Breast Cancer, Nuclear Receptor, Cyclin D1, Cell Proliferation
Publications
  • Articles:

  • Vladimir MP, Zhou J, Shirley LA, Wu K, Vadlamudi RK, Kumar R, Jiang J, Quong J, Rui H, Wang C, and Pestell RG. The Cell Fate Determination Factor DACH1 is expressed in Estrogen Receptor-± (ER±) positive breast cancer and represses ER± signaling. Cancer Research. (In press).

  • Nan F, Lü Q, Zhou J, Cheng L, Popov VM, Wei S, Kong B, Pestell RG, Lisanti MP, Jiang J, Wang C. DACH1 and Cyclin D1 Expression in Endometrial Cancer Progression. Cancer Biology & Therapy. (In press)

  • Liu M, Ju X, Willmarth NE, Casimiro MC, Ojeifo J, Sakamaki T, Katiyar S, Jiao X, Popov VM, Yu Z, Wu K, Joyce D, Wang C, and Pestell RG. NFkB enhances ErbB2-induced mammary tumorigenesis and neoangiogenesis in vivo. Am J Pathol. (In press).

  • Witkiewicz AK, Casimiro MC, Dasgupta A, Mercier I, Wang C, Bonuccelli G, Jasmin J, Frank PG, Pestell RG, Kleer CG, Sotgia F and Lisanti MP. Towards a new stromal-based classification system for human breast cancer prognosis and therapy. Cell Cycle. Volume: 8 | Issue: 11. (In press).

  • Sotgia F, Del Galdo F, Casimiro MC, Bonuccelli G, Mercier I, Whitaker-Menezes D, Daumer KM, Zhou J, Wang C, Katiyar S, Xu H, Bosco E, Quong AA, Aronow B, Witkiewicz AK, Minetti C, Frank PG, Jimenez SA, Knudsen ES, Pestell RG, Lisanti MP. Caveolin-1-/- null mammary stromal fibroblasts share characteristics with human breast cancer-associated fibroblasts. Am J Pathol. 2009 Mar; 174(3):746-61.

  • Sotgia F, Casimiro MC, Bonuccelli G, Liu M, Whitaker-Menezes D, Er O, Daumer KM, Mercier I, Witkiewicz AK, Minetti C, Capozza F, Gormley M, Quong AA, Rui H, Frank PG, Milliman JN, Knudsen ES, Zhou J, Wang C, Pestell RG, Lisanti MP. Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation. Am J Pathol. 2009 Feb; 174(2):613-29.

  • Yu Z, Wang C, Wang M, Li Z, Casimiro MC, Liu M, Wu K, Whittle J, Ju X, Hyslop T, McCue P, Pestell RG. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol. 2008 Aug 11;182 (3):509-17.

  • Mercier I, Casimiro MC, Wang C, Rosenberg AL, Quong J, Allen KG, Danilo C, Sotgia F, Bonnucelli G, Jasmin JF, Xu H, Bosco E, Aronow B, Witkiewicz A, Pestell RG, Knudsen ES, Lisanti MP.Human Breast Cancer-Associated Fibroblasts (CAFs) Show Caveolin-1 Down-regulation and RB Tumor Suppressor Functional Inactivation: Implications for the Response to Hormonal Therapy. Cancer Biol Ther. 2008 Apr 30;7(8) [Epub ahead of print]

  • Rao M, Casimiro MC, Lisanti MP, D'Amico M, Wang C, Shirley LA, Leader JE, Liu M, Stallcup M, Engel DA, Murphy DJ, Pestell RG.Inhibition of cyclin D1 gene transcription by Brg-1.Cell Cycle. 2008 Mar;7(5):647-55. Epub 2007 Dec 12.

  • Jiao X, Katiyar S, Liu M, Mueller SC, Lisanti MP, Li A, Pestell TG, Wu K, Ju X, Li Z, Wagner EF, Takeya T, Wang C, Pestell RG.Disruption of c-Jun Reduces Cellular Migration and Invasion through Inhibition of c-Src and Hyperactivation of ROCK II Kinase.Mol Biol Cell. 2008 Apr; 19(4):1378-1390.

  • Li Z, Wang C*, Jiao X, Katiyar S, Casimiro MC, Prendergast GC, Powell MJ, Pestell RG*. Alternate cyclin D1 mRNA splicing modulates p27KIP1 binding and cell migration. J Biol Chem. J Biol Chem. 2008 Mar 14;283(11):7007-15. (*corresponding author).

  • Ju X, Katiyar S, Wang C, Liu M, Shengwen Li S, Jiao X, Zhou J, Turner J, Lisanti MP, Russell RG, Mueller S, Ojeifo J, Chen WS, Hay N, and Pestell RG. Akt1 governs breast cancer progression in vivo. Natl Acad Sci U S A. 2007 May 1;104(18):7438-43.

  • Li Z, Jiao X, Wang C, Ju X, Lu Y, Yuan L, Lisanti MP, Katiyar S, Pestell RG. Related Articles, Cyclin D1 induction of cellular migration requires p27 (KIP1). Cancer Res. 2006 Oct 15; 66(20):9986-94.

  • Fu M, Liu M, Sauve AA, Jiao X, Zhang X, Powell M, Yang T, Gu W, Avantaggiati ML, Pattabiraman N, Pestell TG, Wang F, Quong A, Wang C, Pestell RG. The Hormonal Control of Androgen Receptor Function through SIRT1. Mol Cell Biol. 2006 Nov; 26(21):8122-35.

  • Wu K, Li A, Rao M, Liu M, Dailey V, Yang Y, Vizio DD, Wang C, Lisanti MP, Sauter G, Russell RG, Cvekl A, Pestell RG. DACH1 is a Cell Fate Determination Factor That Inhibits Cyclin D1 and Breast Tumor Growth. Mol Cell Biol. 2006 Oct; 26(19):7116-29.

  • Wang C, Li Z, Lu Y, Du R, Katiyar S, Yang J, Fu M, Leader JE, Quong A, Novikoff PM, and Pestell RP. Cyclin D1 Repression of NRF-1 Integrates Nuclear DNA Synthesis and Mitochondrial Function. Proc Natl Acad Sci U S A. 2006 Aug 1; 103(31):11567-72.

  • Hulit J, Lee RJ, Li Z, Wang C, Yang J, Quong A, Wu K, Albanese C, Russell R, Di Vizio D, Koff A, Thummala S, Zhang H, Harrell J, Sun H, Muller WJ, Inghirami G, and Pestell RP. p27Kip1 repression of ErbB2-induced mammary tumor growth in transgenic mice involves Skp2 and Wnt/b-catenin signaling. Cancer Res. 2006 (In press).

  • Sakamaki T, Casimiro M, Ju X, Quong A, Katiyar S, Liu M, Jiao X, Li A, Zhang X, Lu Y, Wang C, Nicholson R, Link T, Shemluck M, Yang J, Fricke ST, Novikoff PM, Papanikolaou A, Arnold A, Albanese C and Pestell RG. Cyclin D1 determines Mitochondrial Function In Vivo. Mol Cell Biol. 2006 Jul; 26(14):5449-69.

  • Li Z, Wang C, Jiao X, Lu Y, Fu M, Quong AA, Dye C, Yang J, Dai M, Ju X, Zhang X, Li A, Burbelo P, Stanley R, Pestell RG Cyclin D1 regulates cellular migration through the inhibition of thrombospondin-1 and ROCK signaling. Mol Cell Biol. 2006 Jun; 26(11):4240-56.

  • Yin Y, Yuan H, Wang C, Pattabiraman N, Rao M, Pestell RG, and Glazer RI. 3-Phosphoinositide-Dependent Protein Kinase-1 Activates the Peroxisome Proliferator-Activated Receptor g and Promotes Adipocyte Differentiation. Mol Endocrinol. 2006 Feb; 20(2):268-78.

  • Wang C, Fan S, Li Z, Fu M, Rao M, Ma Y, Lisanti MP, Albanese C, Katzenellenbogen BS, Kushner PJ, Weber B, Rosen EM, and Pestell RG. Cyclin D1 antagonizes BRCA1 repression of estrogen receptor alpha activity. Cancer Res. 2005 Aug 1; 65(15):6557-67.

  • Fu M, Wang C, Rao M, Wu X, Bouras T, Zhang X, Li Z, Jiao X, Yang J, Li A, Perkins ND, Thimmapaya B, Kung AL, Munoz A, Giordano A, Lisanti MP, Pestell RG. Cyclin D1 represses p300 transactivation through a CDK-independent mechanism. J Biol Chem. 2005 Aug 19; 280(33):29728-42.

  • Fu M, Rao M, Bouras T, Wang C, Wu K, Zhang X, Li Z, Yao TP, Pestell RG. Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment. J Biol Chem. 2005 Apr 29; 280(17):16934-41. Epub 2005 Feb 14.

  • Wu K, D'Amico M, Wang C, Albanese C, Pestell RG, Mani S. A study of cytotoxic synergy of UCN-01 and flavopiridol in syngeneic pair of cell lines. Invest New Drugs. 2005 Aug; 23(4):299-309.

  • Hulit J*, Wang C*, Li Z, Albanese C, Rao M, Di Vizio D, Shah S, Byers SW, Mahmood R, Augenlicht LH, Russell R, Pestell RG. Cyclin D1 Genetic Heterozygosity Regulates Colonic Epithelial Cell Differentiation and Tumor Number in ApcMin Mice. Mol Cell Biol. 2004 Sep; 24(17): 7598-611. *Equal contribution

  • Fu M, Rao M, Wu K, Wang C, Zhang X, Hessien M, Yeung YG, Gioeli D, Weber MJ, Pestell RG. The androgen receptor acetylation site regulates cAMP and AKT but not ERK-induced activity. J Biol Chem. 2004 Jul 9; 279(28): 29436-49.

  • Wu K, Yang Y, Wang C, Davoli MA, D'Amico M, Li A, Cveklova K, Kozmik Z, Lisanti MP, Russell RG, Cvekl A, Pestell RG. DACH1 inhibits TGF-beta signaling through binding Smad4. J Biol Chem. 2003 Dec 19; 278(51): 51673-84.

  • Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B, Zhou J, Zafonte B, Goldberg ID, Haddad BR, Pestell RG, Rosen EM. BRCA1 Inhibition of Telomerase Activity in Cultured Cells. Mol Cell Biol. 2003 Dec 1; 23(23): 8668-8690.

  • Fu M, Rao M, Wang C, Sakamaki T, Wang J, Di Vizio D, Zhang X, Albanese C, Balk S, Chang C, Fan S, Rosen E, Palvimo JJ, Janne OA, Muratoglu S, Avantaggiati ML, Pestell RG. Acetylation of Androgen Receptor Enhances Coactivator Binding and Promotes Prostate Cancer Cell Growth. Mol Cell Biol. 2003 Dec 1; 23(23): 8563-8575.

  • Wang C, Pattabiraman N, Zhou JN, Fu M, Sakamaki T, Albanese C, Li Z, Wu K, Hulit J, Neumeister P, Novikoff PM, Brownlee M, Scherer PE, Jones JG, Whitney KD, Donehower LA, Harris EL, Rohan T, Johns DC, Pestell RG. Cyclin D1 repression of peroxisome proliferator-activated receptor gamma expression and transactivation. Mol Cell Biol. 2003 Sep; 23(17): 6159-73.

  • Wu K, Wang C, D'Amico M, Lee RJ, Albanese C, Pestell RG, Mani S. Flavopiridol and trastuzumab synergistically inhibit proliferation of breast cancer cells: association with selective cooperative inhibition of cyclin D1-dependent kinase and Akt signaling pathways. Mol Cancer Ther. 2002 Jul; 1(9): 695-706.

  • Fu M, Wang C, Wang J, Zhang X, Sakamaki T, Yeung YG, Chang C, Hopp T, Fuqua SA, Jaffray E, Hay RT, Palvimo JJ, Janne OA, Pestell RG. Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol Cell Biol. 2002 May; 22(10): 3373-88.

  • Chi Y, Diaz-Griffero F, Wang C, Young JA, Brojatsch J. An NF-kappa B-dependent survival pathway protects against cell death induced by TVB receptors for avian leukosis viruses. J Virol. 2002 Jun; 76(11): 5581-7.

  • Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM. p300 Modulates the BRCA1 inhibition of estrogen receptor activity. Cancer Res. 2002 Jan 1; 62(1): 141-51.

  • Schlegel A, Wang C, Pestell RG, Lisanti MP. Ligand-independent activation of oestrogen receptor alpha by caveolin-1. Biochem J. 2001 Oct 1; 359(Pt 1): 203-10.

  • Reutens AT, Fu M, Wang C, Albanese C, McPhaul MJ, Sun Z, Balk SP, Janne OA, Palvimo JJ, Pestell RG. Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner. Mol Endocrinol. 2001 May; 15(5): 797-811.

  • Wang C, Fu M, D'Amico M, Albanese C, Zhou JN, Brownlee M, Lisanti MP, Chatterjee VK, Lazar MA, Pestell RG. Inhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1. Mol Cell Biol. 2001 May; 21(9): 3057-70.

  • Wang C, Fu M, Angeletti RH, Siconolfi-Baez L, Reutens AT, Albanese C, Lisanti MP, Katzenellenbogen BS, Kato S, Hopp T, Fuqua SA, Lopez GN, Kushner PJ, Pestell RG. Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity. J Biol Chem. 2001 May 25; 276(21): 18375-83.

  • Fan S, Ma YX, Wang C Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM. Role of direct interaction in BRCA1 inhibition of estrogen receptor activity. Oncogene. 2001 Jan 4; 20(1): 77-87.

  • Wang C, Francis R, Harirchian S, Batlle D, Mayhew B, Bassett M, Rainey WE, Pestell RG. The application of high-density microarray for analysis of mitogenic signaling and cell-cycle in the adrenal. Endocr Res. 2000 Nov; 26(4): 807-23.

  • Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L, Ogryzko V, Avantaggiati ML, Pestell RG. p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. J Biol Chem. 2000 Jul 7; 275(27): 20853-60.

  • Schlegel A, Wang C, Katzenellenbogen BS, Pestell RG, Lisanti MP. Caveolin-1 potentiates estrogen receptor alpha (ERalpha) signaling. Caveolin-1 drives ligand-independent nuclear translocation and activation of ERalpha. J Biol Chem. 1999 Nov 19; 274(47): 33551-6.

  • Reviews and Book Chapters:

  • Wang C, Powell MJ, Popov VM, Pestell RG. Acetylation in Nuclear Receptor Signaling and the Role of Sirtuins. Mol Endocrinol. 2007 Dec 28; [Epub ahead of print]

  • Whittle JR, Powell MJ, Popov VM, Shirley LA, Wang C, Pestell RG. Sirtuins, nuclear hormone receptor acetylation and transcriptional regulation.Trends Endocrinol Metab. 2007 Nov;18(9):356-64. Epub 2007 Oct 26. PMID: 17964799 [PubMed - in process]

  • Popov VM, Wang C, Shirley LA, Rosenberg A, Li S, Nevalainen M, Fu M, Pestell RG. The functional significance of nuclear receptor acetylation. Steroids. 2007 Feb 6; [Epub ahead of print]

  • Leader JE, Wang C, Popov VM, Fu M, Pestell RG. Epigenetics and the estrogen receptor. Ann N Y Acad Sci. 2006 Nov; 1089:73-87.

  • Li Z, Wang C, Prendergast G, Pestell RG. Cyclin D1 Functions in Cell Migration. Cell Cycle. 2006 Nov 1;5(21).

  • Leader JE, Wang C, Fu M, Pestell RG. Epigenetic regulation of nuclear steroid receptors. Biochem Pharmacol. 2006 Jul 14; [Epub ahead of print]

  • Wang C, Fu M, Pestell RG. Estrogen receptor acetylation and phosphorylation in hormone responses. Breast Cancer Online. 2005.

  • Hilakivi-Clarke L, Wang C, Kalil M, Riggins R, Pestell RG. Nutritional modulation of the cell cycle and breast cancer. Endocr Relat Cancer. 2004 Dec; 11(4): 603-22.

  • Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: Normal and Abnormal Functions. Endocrinology. 2004 Aug 26

  • Fu M, Wang C, Zhang X, Pestell RG. Biochem Pharmacol. 2004 Sep 15; 68(6): 1199-208.

  • Fu M, Wang C, Zhang X, Pestell RG. Signal Transduction Inhibitors in Cellular Function. Chapter 2, Signal Transduction Protocols, Editor: Robert C. Dickson and Michael D. Mendenhall. Second Edition Humana Press Inc. Totowa, NJ. 2004. Method in Molecular Biology. Vol 284, page15-36.

  • Wang C, Li Z, Fu M, Bouras T, Pestell RG. Signal tranduction mediated by cyclin D1: from mitogens to cell proliferation: A molecular target with therapeutic potential. Rakesh Kumar, ed. Molecular Targeting & Signal Transduction. Kluwer Academic Publisher Cancer Treat Res. 2004;119:217-37.

  • Fu M, Wang C, Zhang X, Pestell RG. Nuclear receptor modifications and endocrine cell proliferation. J. Steroid Biochem. & Mol. Biol. 2003, June; 85 (2-5): 133-8.

  • Wang C, Fu M, Pestell RG. Chapter. Histone acetylation/deacetylation as a regulator of cell-cycle gene expression In the book. "Cell cycle checkpoint control protocols" Methods in Molecular Biology and Medicine (H. Lieberman, ed.), Humana Press, Inc., Totowa, NJ. 2004; 241:207-16.

  • Fu M, Wang C, Wang J, Zafonte BT, Lisanti MP, Pestell RG. Acetylation in hormone signaling and the cell cycle. Cytokine Growth Factor Rev. 2002 Jun; 13(3): 259-76.

  • Wang C, Fu M, Mani S, Wadler S, Senderowicz AM, Pestell RG. Histone acetylation and the cell-cycle in cancer. Front Biosci. 2001 Apr 1; 6:D610-29.

  • Zafonte BT, Hulit J, Amanatullah DF, Albanese C, Wang C, Rosen E, Reutens A, Sparano JA, Lisanti MP, Pestell RG. Cell-cycle dysregulation in breast cancer: breast cancer therapies targeting the cell cycle. Front Biosci. 2000 Dec 1; 5:D938-61.

  • Mani S, Wang C, Wu K, Francis R, Pestell R. Cyclin-dependent kinase inhibitors: novel anticancer agents. Expert Opin Investig Drugs. 2000 Aug; 9(8): 1849-70.

Individual Expertise profile of Chenguang Wang, Ph.D., Copyright © Chenguang Wang, Ph.D..
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