Hormonally Up-regulated Neu-associated Kinase (Hunk): A novel target for breast cancer progression

Published

May 1, 2017

Author(s)

Benjamin A. Neely, Elizabeth Yeh, Joelle S. Zambrano

Abstract

Hormonally Up-regulated Neu-associated Kinase (Hunk) is a kinase that was originally identified in the murine mammary gland and has been shown to be highly expressed in HER2-positive (HER2+) 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) 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+ breast cancer progression, including resistance to HER2 inhibitors, with Hunk potentially acting downstream of HER2 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+ breast cancer patients acquire resistance to HER2 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 kinase's role in both tumorigenesis and drug resistance will be informative. This review focuses on what is currently known about this under-studied kinase, and how targeting Hunk may prove to be a potential therapeutic target for the treatment of breast cancer.

Citation

Pharmacological Research

Volume

119

Pub Type

Journals

Download Paper

https://doi.org/10.1016/j.phrs.2017.02.007

Local Download

Keywords

breast cancer, kinase, resistance, HER2, Hunk

Citation

Neely, B. , Yeh, E. and Zambrano, J. (2017), Hormonally Up-regulated Neu-associated Kinase (Hunk): A novel target for breast cancer progression, Pharmacological Research, [online], https://doi.org/10.1016/j.phrs.2017.02.007 (Accessed April 28, 2024)