Thyroid hormones show not only genomic, but also nongenomic activity, which is related to specific membrane, cytoplasmic and organelle receptors. The best known receptors are located on the alpha-V-beta-3 integrin of cell membrane. Their stimulation results in an activation of mitogen-activated protein kinases (MAPKs) or phosphoinositide 3-kinase (PI3K), which directly leads to an inhibition of apoptosis and increased proliferation of tumor cells, as well as promotes angiogenesis and metastasis formation. In ovarian cancer cells L-thyroxine is proven to be involved in MAPK activation as well as in the up-regulation of expression and enhanced cellular accumulation of programmed death ligand 1 (PD-L1), which results in an inhibition of neoplastic cells apoptosis.

thyroid hormones; ovarian cancer.

Lin HY1, Tang HY, Davis FB, Mousa SA, Incerpi S, Luidens MK, Meng R, Davis PJ Nongenomic regulation by thyroid hormone of plasma membrane ion and small molecule pumps. 2012 Sep;14(76):199-206.

Konturek Fizjologia człowieka. Podręcznik dla studentów medycyny, wyd. II, S Konturek - 2012 - Elsevier Health Sciences

Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. 2010 Apr;31(2):139-70

Davis PJ, Leonard JL, Davis FB Mechanisms of nongenomic actions of thyroid hormone. 2008 May;29(2):211-8

] J.J. Bergh, H.Y. Lin, L. Lansing, S.N. Mohamed, F.B. Davis, S. Mousa, P.J. Davis, Integrin avb3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis, Endocrinology 146 (2005) 2864–2871.

Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Ann Rev Pathol 2009; 4: 127–150.

Tafani M at al, Bridging hypoxia, inflammation and estrogen receptors in thyroid cancer progression. Biomed Pharmacother. 2014 Feb;68(1):1-5. doi: 10.1016

Christine H. Hofschneider, Jonathan S. Berek; Ovarian Cancer: Epidemiology, Biology and Prognostic Factors; Seminars in Surgical Oncology 2000, 19:3-10

La Vecchia C, Ovarian cancer: epidemiology and risk factors. Eur J Cancer Prev. 2017 Jan;26(1):55-62

Lee, J. W., Bae, S. H., Jeong, J. W., Kim, S. H., & Kim, K. W. (2004). Hypoxia-inducible factor (HIF-1) α: its protein stability and biological functions. Experimental & molecular medicine, 36(1), 1-12.

Shinderman-Maman E, Cohen K, Weingarten C, Nabriski D, Twito O, Baraf L, Hercbergs A, Davis PJ, Werner H, Ellis M, Ashur-Fabian O. The thyroid hormone-αvβ3 integrin axis in ovarian cancer: regulation of gene transcription and MAPK-dependent proliferation. Oncogene. 2016 Apr 14;35(15):1977-87.

Weingarten C, Jenudi Y, Tshuva RY, Moskovich D, Alfandari A, Hercbergs A, Davis PJ, Ellis M, Ashur-Fabian O. The Interplay Between Epithelial-Mesenchymal Transition (EMT) and the Thyroid Hormones-αvβ3 Axis in Ovarian Cancer. Horm Cancer. 2018 Feb;9(1):22-32.

Lin HY, Zhang S, West BL, Tang HY, Passaretti T, Davis FB, Davis PJ. Identification of the putative MAP kinase docking site in the thyroid hormone receptor-beta1 DNA-binding domain: functional consequences of mutations at the docking site. Biochemistry. 2003;42:7571–7579.

Rae MT, Gubbay O, Kostogiannou A, Price D, Critchley HO, Hillier SG. Thyroid hormone signaling in human ovarian surface epithelial cells. J Clin Endocrinol Metab. 2007;92:322–327.

Chin YT, Wei PL, Ho Y, Nana AW, Changou CA, Chen YR, Yang YS, Hsieh MT, Hercbergs A, Davis PJ, Shih YJ, Lin HY. Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells. Endocr Relat Cancer. 2018 May;25(5):533-545.

De Craene B, Berx G (2013) Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 13(2):97–110]

C. Weingarten, Y. Jenudi, R. Yair Tshuva, D. Moskovich, A. Alfandari, A. Hercbergs, PJ Davis, M. Ellis, O. Ashur-Fabian The interplay Between Epithelial-Mesenchymal Transition (EMT) and the Thyroid Hormones-αvβ3 Axis in Ovarian Cancer, Horm Cancer. 2018 Feb;9(1):22-32

Albina N Minlikeeva, Jo L Freudenheim, Rikki A Cannioto at al. History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report. Br J Cancer. 2017 Sep 26; 117(7): 1063–1069