Open AccessSmall molecules inhibiting the nuclear localization of YAP/TAZ for chemotherapeutics and chemosensitizers against breast cancers
Author(s) -
Oku Yusuke,
Nishiya Naoyuki,
Shito Toshiya,
Yamamoto Reiichiro,
Yamamoto Yasufumi,
Oyama Chihiro,
Uehara Yoshimasa
Publication year - 2015
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2015.06.007
Subject(s) - cancer research , pazopanib , hippo signaling pathway , breast cancer , cancer , dasatinib , phosphorylation , doxorubicin , cell growth , medicine , biology , chemotherapy , microbiology and biotechnology , biochemistry , sunitinib , myeloid leukemia , imatinib
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.