HUNK Gene Alterations in Breast Cancer

Abstract

Hormonally upregulated neu-associated kinase (HUNK) is a serine/threonine (S/T) protein kinase related to the adenosine monophosphate-activated protein kinase (AMPK) family of kinases. HUNK was originally discovered using a screen to identify kinases expressed in the mouse mammary gland. Therefore, the majority of studies to date have been carried out in models specific to this tissue, and the kinase was named to reflect its mammary gland-specific physiology and pathology. Prior studies show a clear pathogenic role for HUNK in breast cancer. HUNK is upregulated in response to oncogenic HER2/neu and Akt, and there is strong evidence that HUNK is critical for the survival of breast cancer cells. Further evidence shows that inhibiting HUNK using a variety of breast cancer models, including those that are resistant, inhibits tumorigenesis and metastasis. However, HUNK alterations are infrequent. Here, the incidence and consequence of HUNK alterations in breast cancer is reviewed using data mined from the online database cBioPortal and considered in relation to prior research studies.

Identification and characterization of a potent and selective HUNK inhibitor for treatment of HER2+ breast cancer

“…Data mined from Clinical Proteomic Tumor Analysis Consortium (CPTAC), shows that Rubicon is over-represented in samples with HUNK gene alterations compared to those without HUNK gene alterations (cBioportal) and that the HUNK altered group also showed higher levels of Rubicon phosphorylation. 11 This continues to provide evidence establishing that HUNK has a pro-autophagy function within breast cancer and that HUNK phosphorylation of Rubicon at S92 could be important for further understanding the role of HUNK in HER2+ breast cancer and autophagy. However, the role of Rubicon phosphorylation in HER2+ breast cancer has not been determined.…”

HUNK as a key regulator of tumor-associated macrophages in triple negative breast cancer

“…When we looked at the genomic and proteomic data, we found that immune system pathways including chemokine and cytokine signaling were significantly altered in tumors that had HUNK gene alterations compared to those that did not, suggesting that HUNK may have a role in breast cancer tumor immunity. 27 Chemokines and cytokines are known for their multifunctional role in cancer by affecting immune-cell infiltration and function in the TME, including macrophages, and for their effect on breast cancer growth and metastasis. Therefore, in this study, we aimed to evaluate the role of HUNK in tumor immunity.…”