Browsing by Subject "Authophagy"

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    Identification and characterization of a potent and selective HUNK inhibitor for treatment of HER2+ breast cancer
    (Elsevier, 2024) Dilday, Tinslee; Abt, Melissa; Ramos-Solís, Nicole; Dayal, Neetu; Larocque, Elizabeth; Oblak, Adrian L.; Sintim, Herman O.; Yeh, Elizabeth S.; Pharmacology and Toxicology, School of Medicine
    Human epidermal growth factor receptor 2 (HER2)-targeted agents have proven to be effective, however, the development of resistance to these agents has become an obstacle in treating HER2+ breast cancer. Evidence implicates HUNK as an anti-cancer target for primary and resistant HER2+ breast cancers. In this study, a selective inhibitor of HUNK is characterized alongside a phosphorylation event in a downstream substrate of HUNK as a marker for HUNK activity in HER2+ breast cancer. Rubicon has been established as a substrate of HUNK that is phosphorylated at serine (S) 92. Findings indicate that HUNK-mediated phosphorylation of Rubicon at S92 promotes both autophagy and tumorigenesis in HER2/neu+ breast cancer. HUNK inhibition prevents Rubicon S92 phosphorylation in HER2/neu+ breast cancer models and inhibits tumorigenesis. This study characterizes a downstream phosphorylation event as a measure of HUNK activity and identifies a selective HUNK inhibitor that has meaningful efficacy toward HER2+ breast cancer.