Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis
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Show full item recordEditorial
Cell Press
Date
2022-11-15Referencia bibliográfica
Rehana Qureshi... [et al.]. Estrone, the major postmenopausal estrogen, binds ERa to induce SNAI2, epithelial-to-mesenchymal transition, and ER+ breast cancer metastasis, Cell Reports, Volume 41, Issue 7, 2022, 111672, ISSN 2211-1247, [https://doi.org/10.1016/j.celrep.2022.111672]
Sponsorship
United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1R01CA210440-01A1; Florida Breast Cancer Foundation; Breast Cancer Research Foundation; Susan G. Komen Breast Cancer Foundation PDF16380958; Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2020-119502RJ-I00; UGR-FEDER program E-CTS654-UGR20Abstract
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.