cancers Article Ouabain and Digoxin Activate the Proteasome and the Degradation of the ERα in Cells Modeling Primary and Metastatic Breast Cancer 1, 1, 2 3 Claudia Busonero y, Stefano Leone y, Fabrizio Bianchi , Elena Maspero , Marco Fiocchetti 1, Orazio Palumbo 4 , Manuela Cipolletti 1, Stefania Bartoloni 1 and Filippo Acconcia 1,* 1 Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146 Rome, Italy;
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[email protected] (S.B.) 2 Cancer Biomarkers Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo (FG), Italy;
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[email protected]; Tel.: +39-065-733-6320; Fax: +39-065-733-6321 These authors contributed equally to this work. y Received: 25 November 2020; Accepted: 17 December 2020; Published: 19 December 2020 Simple Summary: Breast cancer (BC) treatment relies on the detection of the estrogen receptor α (ERα). ERα-expressing BC patients are treated with anti-estrogen drugs (i.e., tamoxifen and fulvestrant). Despite their proven efficacy, these drugs cause serious side effects in a significant fraction of the patients, including both tumor insurgence in secondary organs, and resistant phenotypes, which result in a relapsing disease with scarce treatment options.