Estradiol and Estrone Have Different Biological Functions to Induce NF-kappa B-Driven Inflammation, EMT and Stemness in ER plus Cancer Cells Díaz Ruano, Ana Belén Martínez Alarcón, Nuria Perán, Macarena Benabdellah, Karim García Martínez, María de los Ángeles Preda, Ovidiu Ramírez Tortosa, César Luis González hernández, Andrea Marchal Corrales, Juan Antonio Picón Ruiz, Manuel ER+ cancer Estradiol Estrone Inflammation NF-KB HSD17B In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-tomesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17 -Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases. 2023-03-06T08:34:41Z 2023-03-06T08:34:41Z 2023-01-07 info:eu-repo/semantics/article Diaz-Ruano, A.B... [et al.]. Estradiol and Estrone Have Different Biological Functions to Induce NF- B-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells. Int. J. Mol. Sci. 2023, 24, 1221. [https://doi.org/10.3390/ijms24021221] https://hdl.handle.net/10481/80411 10.3390/ijms24021221 eng http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Atribución 4.0 Internacional MDPI