RESEARCH INTERESTS
Role of Steroid Hormones in Tumor Angiogenesis; Molecular mechanisms of steroid hormone/anti-hormone action.
The main aim of our laboratory is to identify steroid hormone dependent molecular targets that can be utilized for anti-angiogenic therapy of endocrine dependent disease such as the breast, uterine, and prostate cancer.
Formation of new blood vessels, or angiogenesis, is crucial for normal processes such as embryonic development, wound healing, and endometrial regeneration following menstruation. Angiogenesis is also essential for tumor growth, and metastasis. An emerging field in cancer therapeutics is the targeting of new blood vessels to curtail tumor growth. Our laboratory is currently focusing on the role of steroid hormones, clinically relevant anti-hormones, and endocrine-disruptors to understand the basic mechanisms involved in hormone driven angiogenesis in breast, and uterine tissue. We are currently focusing on the role of estrogens, progestins, and their nuclear receptors in controlling the expression of potent angiogenic growth factors (e.g VEGF and its receptors) at both molecular and cellular level.
Another focus of the laboratory is to investigate the molecular mechanisms of steroid hormone action at the level of gene transcription. We are especially interested in the role of natural and synthetic ligands that have diverse biological effects in different target tissues (e.g SERMS such as tamoxifen). Many synthetic ligands (agonists /antagonists) are consumed by millions of women all over the world for oral contraception, hormone replacement therapy, or treatment of breast cancer. Consumption of some of these ligands lead to increased risk of breast and/or uterine abnormalities, including cancer. We anticipate that understanding the molecular basis/pharmacology of ligand-nuclear receptor interactions will allow development of better therapeutic modalities for treatment of hormone dependent tumors, as well as endometriosis, osteoporosis, and infertility.
SELECTED PUBLICATIONS
Krumenacker, J. S., Hyder, S. M. and Murad, F. (2001). Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus. Proc Natl Acad Sci. 98: 717-722.
Hyder, S. M., Chiappetta, C. and Stancel, G. M. (2001) Pharmacological and endogenous progestins induce vascular endothelial growth factor expression in human breast cancer cells. Int J Cancer 92:469 473.
Hyder, S. M. and Stancel, G. M. (2002) Pure antiestrogen ICI 182,780 inhibits progesterone induced VEGF induction in breast cancer cells. Cancer Lett 181: 47-53.
Hyder, S. M. (2002). The role of steroid hormones on the regulation of vascular endothelail growth factor. Am J Pathology. 161: 345-346
Uray, I., Liang, Y. and Hyder, S. M. (2004). Estradiol Down-regulates CD36 expression in human breast cancer cells. Cancer Lett. 207: 101-107.
Wu, J., Richer, J., Horwitz, K. B. and Hyder, S. M. (2004). Progestin-dependent induction of VEGF in uman breast cancer cells: preferential regulation by progesterone receptor B. Cancer Res 64:2238-2244.
Wu, J., Brandt, S. and Hyder, S. M. (2005) Ligand- and cell-specific effects of signal transduction pathway inhibitors on progestin-induced VEGF levels in human breast cancer cells Molecular Endocrinology 19:312-326
Liang, Y., Wu, J. and Hyder, S. M. (2005). p53-dependent inhibition of progestin-induced VEGF expression in human breast cancer cells. J. Steroid Biochemistry and Molecular Biology 93:173-182.
Liang, Y. and Hyder, S.M. (2005) Proliferation of Endothelial and Tumor Epithelial Cells by Progestin-Induced VEGF from Human Breast Cancer Cells: Paracrine and Autocrine Effects. Endocrinology 146; 3632-3641.
Wu, J., Liang, Y., Nawaz, Z. and Hyder, S. M. (2005). ICI 182,780 (Faslodex) exhibits partial progestin-like activity in human breast cancer cells expressing increased levels of PRB. Int. J .Oncol. 27:1647-1659.
Zhou, W., Liu, Z., Wu, J., Liu, J., Hyder, S. M., Antoniou, E. and Lubahn, D. B. (2006) Identification and partial characterization of two novel splicing isoforms of human ERR-beta. J Clin Endo Metab. 91:569-79.
Benakanakere, I., Besch-Williford, C., Schnell, J., Brandt, S., Molinolo, A., and Hyder, S. M. (2006) Natural and synthetic progestins accelerate 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mammary tumors and increase angiogenesis in Sprague-Dawley rats. Clin Cancer Res 12::4062-4071.
Hyder, S.M. (2006) Sex-steroid regulation of vascular endothelial growth factor in breast cancer. End Related Cancer. 13: 667-687
Carroll, C. E., Elersieck, M. R. and Hyder, S. M. (2008). Curcumin inhibits medroxyprogesterone acetate induced VEGF from T47-D human breast cancer cells. Menopause 15:570-574.
Benakanakere, I., Besch-Williford, C., Elersieck, M. R.and Hyder, S. M. (2009). Regression of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced and progestin-accelerated mammary tumors in Sprague-Dawley rats by PRIMA-1: A pilot study. End Related Cancer 16:85-98.
Liang, Y., Besch-Williford C. and Hyder, S. M., (2009) PRIMA-1 inhibits growth of breast cancer cells by re-activating mutant p53 protein. Int J Oncology 35:1015-1023.
Carroll, C., Besch-Williford C., Benakanakere, I., Elersieck, M. R. and Hyder, S. M. (2010). Curcumin delays development of DMBA-induced progestin-accelerated mammary tumors. Menopause. 17:178-184.
Liang, Y., Benakanakere, I., Besch-Williford, C. B., Hyder, R. S., Ellersieck, M., Hyder, S. M. (2010). Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice. Menopause 17: 1040-1047.
Benakanakere, I., Carroll, C. E., Besch-Williford, C and Hyder, S. M. (2010). Synthetic progestins differentially promote or prevent DMBA-induced mammary tumors in Sprague-Dawley rats. Cancer Prevention Res 3:1157-1167.
Liang, Y., Besch-Williford., Benakanakere, I., Thorpe, P. E. and Hyder, S. M. (2011) Targeting mutant p53 protein and the tumor vasculature: An effective combination therapy for advanced breast tumors. Breast Cancer Res Treat 125: 407-420.
Mafuvadze, B., Benakanakere, I., Lopez, F., Besch-Williford, C., Ellersieck, M. R. and Hyder, S. M. (2011) Apigenin prevents development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Sprague-Dawley rats. Cancer Prevention Res 4: 1316-1324. PMC3151306
Mafuvadze, B., Liang, Y., Besch-Williford, C. and Hyder, S. M. (2012) Apigenin induces apoptosis and blocks growth of medroxyprogesterone acetate-dependent BT-474 xenograft tumors. Hormones and Cancer, 3:160–171
Carroll, C., Benakanakere, I., Liang, Y., Besch-Williford, C and Hyder, S.M. (2013) An anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. Int. J. Oncology, 42: 179-187.
Mafuvadze, B., Cook, M.T., Zhang, Z., Besch-Williford, C. and Hyder, S.M. (2013). Effects of dietary apigenin on tumor latency, incidence and multiplicity in a medroxyprogesterone acetate-accelerated 7, 12-dimethylbenz(a)anthracene-induced breast cancer model. Nutrition and Cancer, 65:1184-1191.
Liang, Y., Besch-Williford, C., Aebi, J. D., Mafuvadze, B., Cook, M, T., Zou, X. and Hyder, S. M. (2014) Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents: suppression of hormone-dependent breast cancer by the oxidosqualene cyclase inhibitor RO 48-8071. Breast Cancer Res Treat. 146:51-62.
Mafuvadze, B., Liang, Y. and Hyder, S. M. (2014) Cholesterol synthesis inhibitor RO 48-8071 suppresses transcriptional activity of human estrogen and androgen receptor. Oncology Reports. 32:1727-1733.
Cook, M.T., Liang, Y., Besch-Williford, C., Goyette, S., Mafuvadze, B. M. and Hyder, S. M. (2015) Luteolin inhibits progestin-dependent angiogenesis, stem cell-like characteristics, and growth of human breast cancer xenografts. SpringerPlus 4: 444
Liang, Y., Mafuvadze, B., Aebi, J. D. and Hyder, S. M. (2016) Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells. OncoTargets and Therapy 9: 3223–3232
Cook, M. T., Liang, Y., Besch-Williford, C., Hyder, S. M. (2017) Luteolin inhibits metastasis, cell migration, and viability of triple-negative breast cancer cells. Breast Cancer: Targets and Therapy, 9: 9–19.
Goyette, S., Liang, Y., Mafuvadze, B., Cook, M. T., Munir, M. and Hyder, S. M. (2017) Natural and Synthetic Progestins Enrich Cancer Stem Cell-like Cells in Hormone-Responsive Human Breast Cancer Cell Populations In Vitro. Breast Cancer: Targets and Therapy, 9: 347–357
Liang, Y., Goyette, S. and Hyder, S. M. (2017) Cholesterol biosynthesis inhibitor RO 48-8071 reduces progesterone receptor expression and inhibits progestin-dependent stem cell-like cell growth in hormone-responsive human breast cancer cells. Breast Cancer: Targets and Therapy, 9:487-494.
Liang, Y., Mafuvadze, B., Besch-Williford, C. and Hyder, S.M. (2018) A combination of p53-activating APR-246 and phosphatidylserine-targeting antibody potently inhibits tumor development in hormone-dependent mutant p53-expressing breast cancer xenografts. Breast Cancer: Targets and Therapy, 10:53-67
Liang, Y., Besch-Williford, C., Cook, M. T., Belencia, A., Brekken, R.A. and Hyder, S.M. (2019) APR-246 alone and in combination with a phosphatidylserine-targeting antibody inhibits lung metastasis of human triple-negative breast cancer cells in nude mice. Breast Cancer: Targets and Therapy, 11: 249-259.
Liang, Y., Besch-Williford, C., Mafuvadze, B., Brekken, R. and Hyder, S.M. (2020) Combined treatment with p53-activating drug APR-246 and a phosphatidylserine-targeting antibody, 2aG4, inhibits growth of human triple-negative breast cancer xenografts. Cancer Rep Rev 4 (2): 1-10 (DOI: 10.15761/CRR.1000205)
Liang, Y., Zou, X. and Hyder, S. M. (2020) Cholesterol biosynthesis inhibitor RO 48-8071 inhibits viability of aggressive cancer cells. Cancer Rep Rev. 4(4): 1-4.
Liang, Y., Besch-Williford C. and Hyder, S. M. (2022) The estrogen receptor beta agonist liquiritigenin enhances the inhibitory effects of the cholesterol biosynthesis inhibitor RO 48-8071 on hormone-dependent breast-cancer growth. Breast Cancer Res Treat 192, 53–63 https://doi.org/10.1007/s10549-021-06487-y
Liang, Y., Nephew, K. P. and Hyder, S. M. (2023) Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of ovarian cancer cells in vitro and in vivo. Journal of Cancer Science and Clinical Therapeutics 7: 01-08.
Liang, Y and Hyder, S. M. (2023). Liquiritigenin Enhances the Inhibitory Effects of the Cholesterol Biosynthesis Inhibitor RO 48-8071 on Cell Viability in Ovarian-Cancer Cells in Vitro. Journal of Cancer Science and Clinical Therapeutics. 07. 10.26502/jcsct.5079207.
Liang, Y., Cook, M.T and Hyder, S. M. (2024) Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of TNBC In vivo and In vitro. Journal of Cancer Science and Clinical Therapeutics. 8: 119-125.
Liang, Y and Hyder, S. M. (2024) Oxidosqualene Cyclase Inhibitor RO 48-8071increases Functional ERβ Levels in Triple-Negative Breast Cancer Cells. Journal of Cancer Science and Clinical Therapeutics. 8: 216-222.