title: Beta-adrenergic signaling promotes tumor angiogenesis and prostate cancer progression through HDAC2-mediated suppression of thrombospondin-1.
abstract: Chronic behavioral stress and beta-adrenergic signaling have been shown to promote cancer progression, whose underlying mechanisms are largely unclear, especially the involvement of epigenetic regulation. Histone deacetylase-2 (HDAC2), an epigenetic regulator, is critical for stress-induced cardiac hypertrophy. It is unknown whether it is necessary for beta-adrenergic signaling-promoted cancer progression. Using xenograft models, we showed that chronic behavioral stress and beta-adrenergic signaling promote angiogenesis and prostate cancer progression. HDAC2 was induced by beta-adrenergic signaling in vitro and in mouse xenografts. We next uncovered that HDAC2 is a direct target of cAMP response element-binding protein (CREB) that is activated by beta-adrenergic signaling. Notably, HDAC2 is necessary for beta-adrenergic signaling to induce angiogenesis. We further demonstrated that, upon CREB activation, HDAC2 represses thrombospondin-1 (TSP1), a potent angiogenesis inhibitor, through epigenetic regulation. Together, these data establish a novel pathway that HDAC2 and TSP1 act downstream of CREB activation in beta-adrenergic signaling to promote cancer progression.
authors.affiliation: Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hulsurkar
authors.affiliation: Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.|Breast and Thyroid Surgery Center, The Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.|The Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.|The Liaocheng People's Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.|Department of Medical Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: D
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.|The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors.forename: W
authors.initials: W
authors.lastname: Li
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D000318:Adrenergic beta-Agonists; D017362:Cyclic AMP Response Element-Binding Protein; D019700:Thrombospondin 1; D056464:Histone Deacetylase 2