title: Small molecules inhibiting the nuclear localization of YAP/TAZ for chemotherapeutics and chemosensitizers against breast cancers.
abstract: YAP and TAZ oncoproteins confer malignancy and drug resistance to various cancer types. We screened for small molecules that inhibit the nuclear localization of YAP/TAZ. Dasatinib, statins and pazopanib inhibited the nuclear localization and target gene expression of YAP and TAZ. All three drugs induced phosphorylation of YAP and TAZ, and pazopanib induced proteasomal degradation of YAP/TAZ. The sensitivities to these drugs are correlated with dependence on YAP/TAZ in breast cancer cell lines. Combinations of these compounds with each other or with other anti-cancer drugs efficiently reduced cell proliferation of YAP/TAZ-dependent breast cancer cells. These results suggest that these drugs can be therapeutics and chemosensitizers for YAP/TAZ-dependent breast cancers.
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oku
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nishiya
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Shito
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
authors.forename: Reiichiro
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Oyama
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmaceutical Sciences, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Iwate 028-3694, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Uehara
keywords: CTGF, connective tissue growth factor; Combination therapy; Dasatinib; FDA, food and drug administration; GPCR, G-protein coupled receptor; HMG-CoA, hydroxymethylglutaryl-coenzyme A; NF2, neurofibromin 2; Pazopanib; Statins; TAZ; TAZ, transcriptional coactivator with PDZ-binding motif; TEAD, TEA domain family member; YAP; YAP, yes-associated protein