@misc{10481/78958, year = {2022}, month = {11}, url = {https://hdl.handle.net/10481/78958}, abstract = {Recent work showed that the dominant post-menopausal estrogen, estrone, cooperates with nuclear factor kB (NF-kB) to stimulate inflammation, while pre-menopausal 17b-estradiol opposes NF-kB. Here, we show that post-menopausal estrone, but not 17b-estradiol, activates epithelial-to-mesenchymal transition (EMT) genes to stimulate breast cancer metastasis. HSD17B14, which converts 17b-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 17b-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:ERa recruits CBP/p300 to the SNAI2 promoter to induce SNAI2 and stimulate an EMT, while 17b-estradiol:ERa 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 17b-estradiol at menopause, estrone-liganded ERa would promote ER+ breast cancer invasion and metastasis.}, organization = {United States Department of Health & Human Services}, organization = {National Institutes of Health (NIH) - USA 1R01CA210440-01A1}, organization = {Florida Breast Cancer Foundation}, organization = {Breast Cancer Research Foundation}, organization = {Susan G. Komen Breast Cancer Foundation PDF16380958}, organization = {Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2020-119502RJ-I00}, organization = {UGR-FEDER program E-CTS654-UGR20}, publisher = {Cell Press}, title = {Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis}, doi = {10.1016/j.celrep.2022.111672}, author = {Qureshi, Rehana and Picón Ruiz, Manuel and Díaz Ruano, Ana Belén}, }