Browsing by Author "Eblen, Scott T."

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    Correction: HUNK phosphorylates EGFR to regulate breast cancer metastasis
    (Springer Nature, 2021-05) Williams, Carly B.; Phelps-Polirer, Kendall; Dingle, Ivan P.; Williams, Christina J.; Rhett, Matthew J.; Eblen, Scott T.; Armeson, Kent; Hill, Elizabeth G.; Yeh, Elizabeth S.; Pharmacology and Toxicology, School of Medicine
    Erratum for 10.1038/s41388-019-1046-5
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    HUNK phosphorylates EGFR to regulate breast cancer metastasis
    (Springer Nature, 2019-10-09) Williams, Carly B.; Phelps-Polirer, Kendall; Dingle, Ivan P.; Williams, Christina J.; Rhett, Matthew J.; Eblen, Scott T.; Armeson, Kent; Hill, Elizabeth G.; Yeh, Elizabeth S.; Pharmacology and Toxicology, School of Medicine
    Epidermal growth factor receptor (EGFR) is commonly over-expressed in metastatic breast cancer yet metastatic breast cancer is generally resistant to anti-EGFR therapies, and the mechanism for resistance to EGFR inhibitors in this setting is not fully understood. Hormonally up-regulated neu-associated kinase (HUNK) kinase is up-regulated in aggressive breast cancers and is thought to play a role in breast cancer metastasis. However, no studies have been conducted to examine a relationship between EGFR and HUNK in breast cancer metastasis. We performed a kinase substrate screen and identified that EGFR is phosphorylated by HUNK. Our studies show that HUNK phosphorylates EGFR at T654, enhancing receptor stability and downstream signaling. We found that increased phosphorylation of T654 EGFR correlates with increased epithelial to mesenchymal, migration and invasion, and metastasis. In addition, we found that HUNK expression correlates with overall survival and distant metastasis free survival. This study shows that HUNK directly phosphorylates EGFR at T654 to promote metastasis and is the first study to show that the phosphorylation of this site in EGFR regulates metastasis.
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    HUNK Phosphorylates Rubicon to Support Autophagy
    (MDPI, 2019-11-19) Zambrano, Joelle N.; Eblen, Scott T.; Abt, Melissa; Rhett, J. Matthew; Muise-Helmericks, Robin; Yeh, Elizabeth S.; Pharmacology and Toxicology, School of Medicine
    Background: Autophagy is a catabolic cellular recycling pathway that is essential for maintaining intracellular homeostasis. Autophagosome formation is achieved via the coordination of the Beclin-1 protein complex. Rubicon is a Beclin-1 associated protein that suppresses autophagy by impairing the activity of the class III PI3K, Vps34. However, very little is known about the molecular mechanisms that regulate Rubicon function. Methods: In this study, co-immunoprecipitation and kinase assays were used to investigate the ability of Hormonally Upregulated Neu-associated Kinase (HUNK) to bind to and phosphorylate Rubicon. LC3B was monitored by immunofluorescence and immunoblotting to determine whether phosphorylation of Rubicon by HUNK controls the autophagy suppressive function of Rubicon. Results: Findings from this study identify Rubicon as a novel substrate of HUNK and show that phosphorylation of Rubicon inhibits its function, promoting autophagy.