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Overview of Current Findings about the Role of Oestrogen Receptor α in Cancer Cell Signalling Pathways


Authors: P. Voňka;  R. Hrstka
Authors‘ workplace: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in: Klin Onkol 2019; 32(Supplementum 3): 34-38
Category: Review
doi: https://doi.org/10.14735/amko20193S

Overview

Background: Oestrogen receptor α is a key biomarker for breast cancer, and the presence or absence of oestrogen receptor α in breast cancer influences the treatment regimens and patients’ prognosis. Oestrogen receptors α are activated after ligand binding, then translocate into the nucleus and activate the transcription of specific genes. This process is called the genomic effect of oestrogen receptor α. Oestrogen receptor α also has nongenomic effects that are exerted mainly in cytoplasm. Due to the important involvement of oestrogen receptor α in cell signalling, these receptors represent a key target for anticancer therapy.

Purpose: Although oestrogen receptor α was discovered 60 years ago, the corresponding signalling pathways have not yet been fully described due to their complexity. With respect to the considerable extent of oestrogen receptor α signalling, covering all related information is beyond the scope of this review, which is focused mainly on recently discovered aspects of oestrogen receptor α function.

Keywords:

signal transduction – oestrogen receptors


Sources

1. Feng Y, Spezia M, Huang S et al. Breast cancer development and progression: risk factors, cancer stem cells, signal­ing pathways, genomics, and molecular pathogenesis. Genes Dis 2018; 5(2): 77– 106. doi: 10.1016/ j.gendis.2018.05.001.

2. Hardeland R. Mitochondrial hormone receptors –  an emerg­ing field of signal­ing in the cell’s powerhouse. Biomed J Sci Tech Res 2017; 1(6): 1678– 1681. doi: 10.26717/ BJSTR.2017.01.000511.

3. Wakel­ing AE. Similarities and distinctions in the mode of action of different classes of antioestrogens. Endocr Relat Cancer 2000; 7(1): 17– 28.

4. Girgert R, Emons G, Grundker C. Estrogen signal­ing in ERα-negative breast cancer: ERβ and GPER. Front Endocrinol (Lausanne) 2018; 9: 781. doi: 10.3389/ fendo.2018.00781.

5. Safe S, Kim K. Non-classical genomic estrogen receptor (ER)/ specificity protein and ER/ activat­ing protein-1 signal­ing pathways. J Mol Endocrinol 2008; 41(5): 263– 275. doi: 10.1677/ JME-08-0103.

6. Shaulian E. AP-1 –  the Jun proteins: oncogenes or tumor suppressors in disguise? Cell Signal 2010; 22(6): 894– 899. doi: 10.1016/ j.cellsig.2009.12.008.

7. He H, Sinha I, Fan R et al. c-Jun/ AP-1 overexpression reprograms ERα signal­ing related to tamoxifen response in ERα-positive breast cancer. Oncogene 2018; 37(19): 2586– 2600. doi: 10.1038/ s41388-018-0165-8.

8. Hrstka R, Brychtova V, Fabian P et al. AGR2 predicts tamoxifen resistance in postmenopausal breast cancer patients. Dis Markers 2013; 35(4): 207– 212. doi: 10.1155/ 2013/ 761537.

9. Wright TM, Wardell SE, Jasper JS et al. Delineation of a FOXA1/ ERα/ AGR2 regulatory loop that is dysregulated in endocrine ther­apy-resistant breast cancer. Mol Cancer Res 2014; 12(12): 1829– 1839. doi: 10.1158/ 1541-7786.MCR-14-0195.

10. Yasar P, Ayaz G, User SD et al. Molecular mechanism of estrogen-estrogen receptor signaling. Reprod Med Biol 2017; 16(1): 4– 20. doi: 10.1002/ rmb2.12006.

11. Thomas C, Gustafsson JA. The different roles of ER subtypes in cancer bio­logy and ther­apy. Nat Rev Cancer 2011; 11(8): 597– 608. doi: 10.1038/ nrc3093.

12. Zhou W, Slingerland JM. Links between oestrogen receptor activation and proteolysis: relevance to hormone-regulated cancer ther­apy. Nat Rev Cancer 2014; 14(1): 26– 38.

13. Musgrove EA, Sutherland RL. Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 2009; 9(9): 631– 643. doi: 10.1038/ nrc2713.

14. Lin SL, Yan LY, Liang XW et al. A novel variant of ER-α, ER-α36 mediates testosterone-stimulated ERK and Akt activation in endometrial cancer Hec1A cells. Reprod Biol Endocrinol 2009; 7: 102. doi: 10.1186/ 1477-7827-7-102.

15. Tong JS, Zhang QH, Wang ZB et al. ER-α36, a novel variant of ER-α, mediates estrogen-stimulated proliferation of endometrial carcinoma cells via the PKCdelta/ ERK pathway. PLoS One 2010; 5(11): e15408. doi: 10.1371/ journal.pone.0015408.

16. Zhang X, D­ing L, Kang L et al. Estrogen receptor-α 36 mediates mitogenic antiestrogen signal­ing in ER-negative breast cancer cells. PLoS One 2012; 7(1): e30174. doi: 10.1371/ journal.pone.0030174.

17. Kang L, Zhang X, Xie Y et al. Involvement of estrogen receptor variant ER-α36, not GPR30, in nongenomic estrogen signaling. Mol Endocrinol 2010; 24(4): 709– 721. doi: 10.1210/ me.2009-0317.

18. Zhang XT, D­ing L, Kang LG et al. Involvement of ER-α36, Src, EGFR and STAT5 in the biphasic estrogen signal­ing of ER-negative breast cancer cells. Oncol Rep 2012; 27(6): 2057– 2065. doi: 10.3892/ or.2012.1722.

19. Zhang XT, Kang LG, D­ing L et al. A positive feedback loop of ER- α36/ EGFR promotes malignant growth of ER-negative breast cancer cells. Oncogene 2011; 30(7): 770– 780. doi: 10.1038/ onc.2010.458.

20. Acconcia F, Kumar R. Signal­ing regulation of genomic and nongenomic functions of estrogen receptors. Cancer Lett 2006; 238(1): 1– 14. doi: 10.1016/ j.canlet.2005.06.018.

21. Chaudhri RA, Olivares-Navarrete R, Cuenca N et al. Membrane estrogen signal­ing enhances tumorigenesis and metastatic potential of breast cancer cells via estrogen receptor-α36 (ERα36). J Biol Chem 2012; 287(10): 7169– 7181. doi: 10.1074/ jbc.M111.292946.

22. Kang L, Wang ZY. Breast cancer cell growth inhibition by phenethyl isothiocyanate is associated with down-regulation of oestrogen receptor-α36. J Cell Mol Med 2010; 14(6B): 1485– 1493. doi: 10.1111/ j.1582-4934.2009.00877.x.

23. Shi L, Dong B, Li Z et al. Expression of ERα36, a novel variant of estrogen receptor α, and resistance to tamoxifen treatment in breast cancer. J Clin Oncol 2009; 27(21): 3423– 3429. doi: 10.1200/ JCO.2008.17.2254.

24. Zhang X, Wang ZY. Estrogen receptor- α variant, ER-α36, is involved in tamoxifen resistance and estrogen hypersensitivity. Endocrinology 2013; 154(6): 1990– 1998. doi: 10.1210/ en.2013-1116.

25. Wang Q, Jiang J, Y­ing G et al. Tamoxifen enhances stemness and promotes metastasis of ERα36(+) breast cancer by upregulat­ing ALDH1A1 in cancer cells. Cell Res 2018; 28(3): 336– 358. doi: 10.1038/ cr.2018.15.

26. Chen JQ, Yager JD, Russo J. Regulation of mitochondrial respiratory chain structure and function by estrogens/ estrogen receptors and potential physiological/ pathophysiological implications. Biochim Biophys Acta 2005; 1746(1): 1– 17. doi: 10.1016/ j.bbamcr.2005.08.001.

27. Scarpulla RC. Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 2006; 97(4): 673– 683. doi: 10.1002/ jcb.20743.

28. Lone MU, Baghel KS, Kanchan RK et al. Physical interaction of estrogen receptor with MnSOD: implication in mitochondrial O2(.-) upregulation and mTORC2 potentiation in estrogen-responsive breast cancer cells. Oncogene 2017; 36(13): 1829– 1839. doi: 10.1038/ onc.2016.346.

29. Moreira PI, Custodio J, Moreno A et al. Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I lead­ing to mitochondrial failure. J Biol Chem 2006; 281(15): 10143– 10152. doi: 10.1074/ jbc.M510249200.

30. Theodossiou TA, Yannakopoulou K, Aggelidou C et al. Tamoxifen subcellular localization; observation of cell-specific cytotoxicity enhancement by inhibition of mitochondrial ETC complexes I and III. Photochem Photobio­l 2012; 88(4): 1016– 1022. doi: 10.1111/ j.1751-1097.2012.01144.x.

31. Theodossiou TA, Walchli S, Olsen CE et al. Decipher­ing the nongenomic, mitochondrial toxicity of tamoxifens as determined by cell metabolism and redox activity. ACS Chem Biol 2016; 11(1): 251– 262. doi: 10.1021/ acschembio­.5b00734.

32. Theodossiou TA, Ali M, Grigalavicius M et al. Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT-tamoxifen hybrid ther­apy. NPJ Breast Cancer 2019; 5: 13. doi: 10.1038/ s41523-019-0108-8.

33. Rohlenova K, Sachaphibulkij K, Stursa J et al. Selective disruption of respiratory supercomplexes as a new strategy to suppress Her2high breast cancer. Antioxid Redox Signal 2017; 26(2): 84– 103. doi: 10.1089/ ars.2016.6677.

34. Mumcuoglu M, Bagislar S, Yuzugullu H et al. The ability to generate senescent progeny as a mechanism underly­ing breast cancer cell heterogeneity. PLoS One 2010; 5(6): e11288. doi: 10.1371/ journal.pone.0011288.

35. Hubackova S, Davidova E, Rohlenova K et al. Selective elimination of senescent cells by mitochondrial target­ing is regulated by ANT2. Cell Death Differ 2019; 26(2): 276– 290. doi: 10.1038/ s41418-018-0118-3.

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