title: Ubiquitin-activating enzyme is necessary for 17β-estradiol-induced breast cancer cell proliferation and migration.
abstract: The sex steroid hormone 17β-estradiol (E2) regulates breast cancer (BC) cell proliferation and migration through the activation of a plethora of signal transduction cascades (e.g., PI3K/AKT activation) starting after E2 binding to the estrogen receptor alpha (ERα). The activity of the ubiquitin (Ub)-system modulates many physiological processes (e.g., cell proliferation and migration), and recently, a specific inhibitor (Pyr-41) of the Ub-activating enzyme (E1), which works as the activator of the Ub-based signaling, has been identified to prevent the functions of the Ub-system. Here, by using Pyr-41, we studied the involvement of the Ub-system in E2-induced signaling to proliferation and migration of BC cells. Our data indicate that E1 activity is involved in the E2:ERα signaling important for cell proliferation and migration through the modulation of the E2-evoked activation of the PI3K/AKT and the p38/MAPK pathways. These discoveries indicate a new molecular circuitry that can be further explored to define new opportunities for BC treatment.
authors.affiliation: Department of Science, Section Biomedical Sciences and Technology, University Roma Tre, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pesiri
authors.forename: Pierangela
authors.initials: P
authors.lastname: Totta
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
authors.forename: Filippo
authors.initials: F
authors.lastname: Acconcia
mesh_terms: D000704:Analysis of Variance; D001565:Benzoates / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005663:Furans / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D011720:Pyrazoles / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: C523934:4(4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl)-benzoic acid ethyl ester; D001565:Benzoates; D005663:Furans; D011720:Pyrazoles; D004958:Estradiol; D044764:Ubiquitin-Activating Enzymes
keywords: 17β-estradiol; Pyr-41; breast cancer; estrogen receptor; ubiquitin-activating enzyme