Qureshi, RehanaPicon-Ruiz, ManuelSho, MaikoVan Booven, DerekNunes de Paiva, VanessaDiaz-Ruano, Anna BInce, Tan ASlingerland, Joyce2023-05-032023-05-032022-10-25Qureshi R, Picon-Ruiz M, Sho M, Van Booven D, Nunes de Paiva V, Diaz-Ruano AB, et al. Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis. Cell Rep. 2022 Nov 15;41(7):111672.http://hdl.handle.net/10668/22078Recent work showed that the dominant post-menopausal estrogen, estrone, cooperates with nuclear factor κB (NF-κB) to stimulate inflammation, while pre-menopausal 17β-estradiol opposes NF-κB. Here, we show that post-menopausal estrone, but not 17β-estradiol, activates epithelial-to-mesenchymal transition (EMT) genes to stimulate breast cancer metastasis. HSD17B14, which converts 17β-estradiol to estrone, is higher in cancer than normal breast tissue and in metastatic than primary cancers and associates with earlier metastasis. Treatment with estrone, but not 17β-estradiol, and HSD17B14 overexpression both stimulate an EMT, matrigel invasion, and lung, bone, and liver metastasis in estrogen-receptor-positive (ER+) breast cancer models, while HSD17B14 knockdown reverses the EMT. Estrone:ERα recruits CBP/p300 to the SNAI2 promoter to induce SNAI2 and stimulate an EMT, while 17β-estradiol:ERα recruits co-repressors HDAC1 and NCOR1 to this site. Present work reveals novel differences in gene regulation by these estrogens and the importance of estrone to ER+ breast cancer progression. Upon loss of 17β-estradiol at menopause, estrone-liganded ERα would promote ER+ breast cancer invasion and metastasis.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/CP: CancerER+ breast cancerHSD17B14SNAI2adipocytesestrone,17β-estradiolmetastasisFemaleHumans17-Hydroxysteroid DehydrogenasesBreast NeoplasmsEstradiolEstrogen Receptor alphaEstrogensEstroneNF-kappa BPostmenopauseSnail Family Transcription FactorsEpithelial-Mesenchymal TransitionNeoplasm Metastasisresearch article36384125open access17-HidroxiesteroideDeshidrogenasasEstradiolEstronaEstrógenosFN-kappa BFactores de transcripción de la familia SnailTransición epitelial-mesenquimalReceptor alfa de estrógenoPosmenopausiaNeoplasias de la mamaMetástasis de la neoplasiaFemenino10.1016/j.celrep.2022.1116722211-1247PMC9798480http://www.cell.com/article/S2211124722015467/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9798480/pdf