ArticleProceedings of the National Academy of Sciences of the United States of America2013
Hunk negatively regulates c-myc to promote Akt-mediated cell survival and mammary tumorigenesis induced by loss of Pten.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Modulating hormonally upregulated neu-associated kinase (HUNK) activity in breast cancer: The development of HUNK inhibitors.The Journal of pharmacology and experimental therapeutics · 2025Review
- lncSLERT Promotes Liver Metastasis in Colorectal Cancer by Down-Regulating HUNK Expression via RBM15-Mediated m6A Modification.OncoTargets and therapy · 2025Article
- Identification and characterization of a potent and selective HUNK inhibitor for treatment of HER2+ breast cancer.Cell chemical biology · 2024Article
- HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1.Cell death & disease · 2023Article
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- Multi-omics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment.Nature communications · 2022Article
- HUNK Signaling in Metastatic Breast Cancer.Oncoscience · 2020Article
- Integral membrane protein 2A inhibits cell growth in human breast cancer via enhancing autophagy induction.Cell communication and signaling : CCS · 2019Article
- Gene loci associated with insulin secretion in islets from non-diabetic mice.The Journal of clinical investigation · 2019Article
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- Dihydroartemisinin triggers c-Myc proteolysis and inhibits protein kinase B/glycogen synthase kinase 3β pathway in T-cell lymphoma cells.Oncology letters · 2018Article
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- The regulatory role of aberrant Phosphatase and Tensin Homologue and Liver Kinase B1 on AKT/mTOR/c-Myc axis in pancreatic neuroendocrine tumors.Oncotarget · 2017Article
- Hypoxic Stress Decreases c-Myc Protein Stability in Cardiac Progenitor Cells Inducing Quiescence and Compromising Their Proliferative and Vasculogenic Potential.Scientific reports · 2017Article
- Hormonally up-regulated neu-associated kinase: A novel target for breast cancer progression.Pharmacological research · 2017Review
- Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer.Breast cancer research and treatment · 2017Article
- Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Article
- mTORC2 promotes cell survival through c-Myc-dependent up-regulation of E2F1.The Journal of cell biology · 2015Article
- Hunk/Mak-v is a negative regulator of intestinal cell proliferation.BMC cancer · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The protooncogenes Akt and c-myc each positively regulate cell growth and proliferation, but have opposing effects on cell survival. These oncogenes cooperate to promote tumorigenesis, in part because the prosurvival effects of Akt offset the proapoptotic effects of c-myc. Akt's ability to counterbalance c-myc's proapoptotic effects has primarily been attributed to Akt-induced stimulation of prosurvival pathways that indirectly antagonize the effects of c-myc. We report a more direct mechanism by which Akt modulates the proapoptotic effects of c-myc. Specifically, we demonstrate that Akt up-regulates the adenosine monophosphate-associated kinase (AMPK)-related protein kinase, Hormonally up-regulated neu-associated kinase (Hunk), which serves as an effector of Akt prosurvival signaling by suppressing c-myc expression in a kinase-dependent manner to levels that are compatible with cell survival. Consequently, Akt pathway activation in the mammary glands of Hunk(-/-) mice results in induction of c-myc expression to levels that induce apoptosis. c-myc knockdown rescues the increase in apoptosis induced by Hunk deletion in cells in which Akt has been activated, indicating that repression of c-myc is a principal mechanism by which Hunk mediates the prosurvival effects of Akt. Consistent with this mechanism of action, we find that Hunk is required for c-myc suppression and mammary tumorigenesis induced by phosphatase and tensin homolog (Pten) deletion in mice. Together, our findings establish a prosurvival function for Hunk in tumorigenesis, define an essential mechanism by which Akt suppresses c-myc-induced apoptosis, and identify Hunk as a previously unrecognized link between the Akt and c-myc oncogenic pathways.
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