Hypoxia inhibits HUNK kinase activity to induce epithelial-mesenchymal transition.

Hypoxia is a common hallmark of cancer and plays a crucial role in promoting epithelial-mesenchymal transition (EMT). Hormonally Upregulated Neu-associated Kinase (HUNK) regulates EMT through its kinase activity. However, whether hypoxia is involved in HUNK-mediated EMT is incompletely understood. This study unveils an association between HUNK kinase activity and hypoxia in colorectal cancer (CRC). Importantly, hypoxia does not alter the expression levels of HUNK, but directly affects the phosphorylation levels of downstream proteins with indication of HUNK activity. Functionally, the upregulation of migration, invasion, and expression of EMT markers in CRC cells under hypoxic conditions can be attributed, in part, to the downregulation of HUNK-mediated phosphorylation of downstream proteins. These findings highlight the intricate relationship between HUNK, hypoxia and the molecular mechanisms of cancer EMT. Understanding these mechanisms may provide valuable insights into therapeutic targets for inhibiting cancer metastasis.

• Publication year

  2023

• Venue

  Biochemical and Biophysical Research Communications - BBRC

• Publication date

  2023-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.bbrc.2023.09.074PMID 37793312
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1

  2023cited by this paper
• LCDR regulates the integrity of lysosomal membrane by hnRNP K–stabilized LAPTM5 transcript and promotes cell survival

  2022cited by this paper
• Hallmarks of Cancer: New Dimensions.

  2022cited by this paper
• Linking EMT programmes to normal and neoplastic epithelial stem cells

  2021cited by this paper
• Activation of AMPK under Hypoxia: Many Roads Leading to Rome

  2020cited by this paper
• DMDRMR-Mediated Regulation of m6A-Modified CDK4 by m6A Reader IGF2BP3 Drives ccRCC Progression

  2020cited by this paper
• Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy

  2020cited by this paper
• Molecular landmarks of tumor hypoxia across cancer types

  2019cited by this paper
• Betulinic acid inhibits stemness and EMT of pancreatic cancer cells via activation of AMPK signaling

  2018cited by this paper
• Hypoxia induced EMT: A review on the mechanism of tumor progression and metastasis in OSCC.

  2018cited by this paper
• AMPK reverses the mesenchymal phenotype of cancer cells by targeting the Akt-MDM2-Foxo3a signaling axis.

  2014cited by this paper
• Molecular mechanisms of epithelial–mesenchymal transition

  2014cited by this paper
• Hunk negatively regulates c-myc to promote Akt-mediated cell survival and mammary tumorigenesis induced by loss of Pten

  2013cited by this paper
• Hunk is required for HER2/neu-induced mammary tumorigenesis.

  2011cited by this paper
• HUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1

  2010cited by this paper
• The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis

  2009cited by this paper
• Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells.

  2008cited by this paper
• A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development.

  1997cited by this paper
• Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.

  1995cited by this paper
• Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.

  1991cited by this paper

• Construction and verification of a prognostic model of neutrophil-related genes in clear cell renal cell carcinoma

  2026influential citation
• Modulating hormonally upregulated neu-associated kinase (HUNK) activity in breast cancer: The development of HUNK inhibitors.

  2025cites this paper