title: Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.
abstract: Hormonally up-regulated neu-associated Kinase (Hunk) is a protein kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in Human Epidermal Growth Factor Receptor 2 positive (HER2+/ErbB2+) breast cancer cell lines as well as MMTV-neu derived mammary tumor cell lines. However, the physiological role of Hunk has been largely elusive since its identification. Though Hunk is predicted to be a Serine/Threonine (Ser/Thr) protein kinase with homology to the SNF1/AMPK family of protein kinases, there are no known Hunk substrates that have been identified to date. Recent work demonstrates a role for Hunk in HER2+/ErbB2+breast cancer progression, including drug resistance to HER2/ErbB2 inhibitors, with Hunk potentially acting downstream of HER2/ErbB2 and the PI3K/Akt pathway. These studies have collectively shown that Hunk plays a vital role in promoting mammary tumorigenesis, as Hunk knockdown via shRNA in xenograft tumor models or crossing MMTV-neu or Pten-deficient genetically engineered mouse models into a Hunk knockout (Hunk-/-) background impairs mammary tumor growth in vivo. Because the majority of HER2+/ErbB2+breast cancer patients acquire drug resistance to HER2/ErbB2 inhibitors, the characterization of novel drug targets like Hunk that have the potential to simultaneously suppress tumorigenesis and potentially enhance efficacy of current therapeutics is an important facet of drug development. Therefore, work aimed at uncovering specific regulatory functions for Hunk that could contribute to this protein kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied protein kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer.
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina Charleston, SC, USA. Electronic address: zambrano@musc.edu.
authors.forename: Joelle N
authors.initials: JN
authors.lastname: Zambrano
authors.affiliation: Marine Biochemical Sciences, National Institute of Standards and Technology, Charleston, SC, USA. Electronic address: benjamin.neely@nist.gov.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Neely
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina Charleston, SC, USA. Electronic address: yeh@musc.edu.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Yeh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017346:Protein Serine-Threonine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C549065:HUNK protein, human
keywords: Breast cancer; Drug resistance; HER2/ErbB2; Hunk; Protein kinase