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

Jefferson
Associate Professor
Thomas Jefferson University
Jefferson Medical College
Department of Stem Cell Biology and Regenerative Medicine
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, colon cancer, hepatocellular carcinoma, hormone nuclear receptor, oncogene, cyclin D1, cell proliferation, lipogenesis, cell fate determination
Publications
  • Publications (since 2006)

  • Research Articles:

  • 1. 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.

  • 2. 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.

  • 3. 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.

  • 4. 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 Sep 1;66(17):8529-41.

  • 5. 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.

  • 6. 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.

  • 7. 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.

  • 8. 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.

  • 9. 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.

  • 10. 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. 2008 Mar 14;283(11):7007-15. (*Corresponding author).

  • 11. 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.

  • 12. 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.

  • 13. 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).

  • 14. 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.

  • 15. 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.

  • 16. 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.

  • 17. 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. 2009 Jun 1;8(11):1654-8.

  • 18. 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. 2009 May;174(5):1910-20.

  • 19. Liu M, Casimiro MC, Wang C, Shirley LA, Jiao X, Katiyar S, Ju X, Li Z, Yu Z, Zhou J, Johnson M, Fortina P, Hyslop T, Windle JJ, Pestell RG. p21CIP1 Governs Oncogene-Dependent Breast Tumor Epithelial Mesenchymal Transformation In Vivo. Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19035-9. Epub 2009 Oct 26.

  • 20. Nan F, Lü Q, Zhou J, Cheng L, Popov VM, Wei S, Kong B, Pestell RG, Lisanti MP, Jiang J, Wang C. Altered expression of DACH1 and cyclin D1 in endometrial cancer. Cancer Biol Ther. 2009 Aug;8(16):1534-9. Epub 2009 Aug 8. (*Corresponding author).

  • 21. Zhou J, Zhang W, Liang B, Casimiro MC, Whitaker-Menezes D, Wang M, Lisanti MP, Lanza-Jacoby S, Pestell RG, Wang C. PPARgamma Activation Induces Autophagy in Breast Cancer Cells. Int J Biochem Cell Biol. 2009 Nov;41(11):2334-42. Epub 2009 Jun 26. (*Corresponding author).

  • 22. Popov VM, Zhou J, Shirley LA, Quong J, Yeow WS, Wright JA, Wu K, Rui H, Vadlamudi RK, Jiang J, Kumar R, Wang C, Pestell RG. The Cell Fate Determination Factor DACH1 is expressed in Estrogen Receptor-± (ER±) positive breast cancer and represses ER± signaling. Cancer Res. 2009 Jul 15;69(14):5752-60.

  • 23. Genander M, Halford MM, Yu Z, Martling A, Xu NJ, Greicius G, Chumley MJ, Zdunek S, Wang C, Holm T, Pettersson S, Pestell RG, Henkemeyer M and Frisén J. Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell. 2009 Nov 13;139(4):679-92.

  • 24. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. The Reverse Warburg Effect: Aerobic Glycolysis in Cancer Associated Fibroblasts and the Tumor Stroma. Cell Cycle. 2009 Dec;8(23):3984-4001

  • 25. Tian L, Zhou J, Casimiro MC, Liang B, Ojeifo JO, Wang M, Hyslop T, Wang C*, Pestell RG. Activation of Peroxisome Proliferator-activated Receptor g Promotes Tumor Growth by Enhancing Angiogenesis. Cancer Res. 2009 Dec 15;69(24):9236-44. (*Corresponding author).

  • 26. Thakur ML, Devadhas D, Zhang K, Pestell RG, Wang C, McCue P, Wickstrom E. Imaging Spontaneous MMTVneu Transgenic Murine Mammary Tumors: Targeting Metabolic Activity Versus Genetic Products. J Nucl Med. 2010 Jan;51(1):106-11.

  • 27. Zhong Z, Yeow WS, Zou C, Wassell R, Wang C, Pestell RG, Quong JN, Quong AA. Cyclin D1/cyclin dependent kinase 4 interacts with filamin A and affects the migration and invasion potential of breast cancer cells. Cancer Res. 2010 Mar 1;70(5):2105-14.

  • 28. Zhou J, Wang C*, Wang Z, Dampier W, Wu K, Casimiro MC, Chepelev I, Popov VM, Quong A, Tozeren A, Zhao K, Lisanti MP, Pestell RG*. Attenuation of Forkhead Signaling by the Retinal Determination Factor DACH1. Proc Natl Acad Sci U S A. 2010 Mar 29. [Epub ahead of print] (*Corresponding author).

  • 29. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, Martinez-Outschoorn UE, Howell A, Sotgia F, Lisanti MP. Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: Similarities with oxidative stress, inflammation, Alzheimer's disease, and "Neuron-Glia Metabolic Coupling". Aging (Albany NY). 2010 Apr;2(4):185-99.

  • 30. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the "reverse Warburg effect": A transcriptional informatics analysis with validation. Cell Cycle. 2010 Jun 22;9(11).

  • 31. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, Whitaker-Menezes D, Daumer KM, Lin Z, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Knudsen ES, Sotgia F, Lisanti MP. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle. 2010 Aug 28;9(16).

  • 32. Li Z, Jiao X, Wang C, Shirley LA, Elsaleh H, Dahl O, Wang M, Soutoglou E, Knudsen ES, Pestell RG. Alternative Cyclin D1 Splice Forms Differentially Regulate the DNA Damage Response. Cancer Res. 2010 Oct 12. [Epub ahead of print]

  • 33. Chiavarina B, Whitaker-Menezes D, Migneco G, Martinez-Outschoorn UE, Pavlides S, Howell A, Tanowitz HB, Casimiro MC, Wang C, Pestell RG, Grieshaber P, Caro J, Sotgia F, Lisanti MP. HIF1-alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: Autophagy drives compartment-specific oncogenesis. Cell Cycle. 2010 Sep;9(17):3534-51. Epub 2010 Sep 4.

  • 34. Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, Frank PG, Casimiro MC, Wang C, Pestell RG, Martinez-Outschoorn UE, Howell A, Sotgia F, Lisanti MP. The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle. 2010 Sep;9(17):3485-505.

  • 35. Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Caro J, Lisanti MP, Sotgia F. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFºB activation in the tumor stromal microenvironment. Cell Cycle. 2010 Sep;9(17):3515-33. Epub 2010 Sep 9.

  • 36. Li Z, Jiao X, Wang C, Shirley LA, Elsaleh H, Dahl O, Wang M, Soutoglou E, Knudsen ES, Pestell RG. Alternative Cyclin D1 Splice Forms Differentially Regulate the DNA Damage Response. Cancer Res. 2010 Oct 12. [Epub ahead of print]

  • 37. Zhou J, Liu Y, Zhang W, Popov VM, Wang M, Pattabiraman N, Suñe C, Cvekl A, Wu K, Jiang J, Wang C*, Pestell RG. Transcription elongation regulator 1 is a co-integrator of the cell fate determination factor Dachshund homolog 1. J Biol Chem. 2010 Oct 18. [Epub ahead of print] (*Corresponding author).

  • 38. Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Trimmer C, Tsirigos A, Migneco G, Witkiewicz AK, Balliet R, Mercier I, Wang C, Flomenberg N, Howell A, Lin Z, Caro J, Pestell RG, Sotgia F, Lisanti MP. The autophagic tumor stroma model of cancer or "battery-operated tumor growth": A simple solution to the autophagy paradox. Cell Cycle. 2010 Nov;9(21):4297-306. Epub 2010 Nov 30.

  • 39. Gaughan L, Stockley J, Wang N, McCracken SR, Treumann A, Armstrong K, Shaheen F, Watt K, McEwan IJ, Wang C, Pestell RG, Robson CN.Regulation of the androgen receptor by SET9-mediated methylation. Nucleic Acids Res. 2011 Mar;39(4):1266-79.

  • 40. Powell MJ, Casimiro MC, Cordon-Cardo C, He X, Yeow WS, Wang C, McCue P, McBurney MW, Pestell RG. Disruption of a Sirt1 Dependent Autophagy Checkpoint in the Prostate Results in Prostatic Intraepithelial Neoplasia Lesion Formation. Cancer Res. 2011 Feb 1;71(3):964-75.

  • 41. Meng H, Tian L, Zhou J, Li Z, Jiao X, Li WW, Plomann M, Xu Z, Lisanti MP, Wang C*, Pestell RG*. PACSIN 2 represses cellular migration through direct association with cyclin D1 but not its alternate splice form cyclin D1b. Cell Cycle. 2011 Jan 1;10(1):73-81. (*Corresponding author).

  • 42. Martinez-Outschoorn UE, Prisco M, Ertel A, Tsirigos A, Lin Z, Pavlides S, Wang C, Flomenberg N, Knudsen ES, Howell A, Pestell RG, Sotgia F, Lisanti MP. Ketones and lactate increase cancer cell "stemness," driving recurrence, metastasis and poor clinical outcome in breast cancer: Achieving personalized medicine via Metabolo-Genomics. Cell Cycle. 2011 Apr 15;10(8):1271-86.

  • 43. Pan X*, Zhou T*, Tai YH*, Wang C, Zhao J, Cao Y, Zhang PJ, Yuan Chen Y, Yu M, Li HY, Li AL, Gao YF, Liang B, Zhang WN, Zhen C, Bai ZF, Gong WL, Wei LX, and Zhang XM. Elevated expression of CUEDC2 protein confers endocrine resistance in breast cancer. Nature Medicine. 2011.

  • Reviews and Book Chapters:

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

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

  • 46. 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.

  • 47. 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]

  • 48. 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.

  • 49. Wang C, Powell MJ, Popov VM, Pestell RG. Acetylation in Nuclear Receptor Signaling and the Role of Sirtuins. Mol Endocrinol. 2008 Mar;22(3):539-45.

  • 50. Popov VM, Wu K, Zhou J, Powell MJ, Mardon G, Wang C, Pestell RG. The Dachshund gene in development and hormone-responsive tumorigenesis. Trends Endocrinol Metab. 2010 Jan;21(1):41-9. Epub 2009 Nov 5.

  • 51. Yu Z, Baserga R, Chen L, Wang C, Lisanti MP, Pestell RG. microRNA, Cell Cycle, and Human Breast Cancer. Am J Pathol. 2010 Mar;176(3):1058-64.

  • 52. Wang C, Tian L, Popov VM, Pestell RG. Acetylation and Nuclear Receptor Action. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):91-100.

  • 53. Wang C, Lisanti MP, Liao DJ. Reviewing once more the c-myc and Ras collaboration: Converging at the cyclin D1-CDK4 complex and challenging basic concepts of cancer biology. Cell Cycle. 2011 Jan 1;10(1). [Epub ahead of print]

  • 54. Wang C, Tai Y, Lisanti MP, Liao DJ. c-Myc induction of programmed cell death may contribute to carcinogenesis: A perspective inspired by several concepts of chemical carcinogenesis. Cancer Biol Ther. 2011 Apr 1;11(7). [Epub ahead of print]

Individual Expertise profile of Chenguang Wang, Ph.D., Copyright © Chenguang Wang, Ph.D..
Last Updated by Chenguang Wang, Ph.D. : Monday, June 13, 2011 5:33:54 PM


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