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Mnk mediates integrin α6β4-dependent eIF4E phosphorylation and translation of VEGF mRNA

Nadejda L Korneeva1, Young Hwa Soung, Hong Im Kim

  • 1Department of Emergency Medicine, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. nkorne@lsuhsc.edu

Molecular Cancer Research : MCR
|November 5, 2010
PubMed

Insights

Integrin α6β4 controls cancer mRNA translation via Mnk1 kinase, which phosphorylates eIF4E. Inhibiting Mnk1 blocks VEGF mRNA translation, suggesting Mnk1 as a therapeutic target in high integrin α6β4 cancers.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Integrin α6β4 is known to influence cancer-related mRNA translation via eIF4E.
  • The role of the Ser/Thr kinase Mnk in cancer progression is established, but its connection to integrin activity is unclear.

Purpose of the Study:

  • To investigate the link between integrin α6β4 and Mnk activity in regulating mRNA translation.
  • To elucidate the signaling pathway downstream of integrin α6β4 that affects Mnk1 and eIF4E.

Main Methods:

  • Investigated integrin α6β4 signaling pathways.
  • Assessed Mnk1 activity and its downstream effects on eIF4E phosphorylation.
  • Utilized Mnk1 inhibition (CGP57380) and downregulation (shRNA) to study VEGF mRNA translation.

Main Results:

  • Identified Mnk1 as a downstream effector of integrin α6β4, mediating signaling for translational control.
  • Demonstrated that integrin α6β4 signals through MEK and p38 MAPK to enhance Mnk1 and eIF4E phosphorylation.
  • Showed that Mnk1 inhibition or downregulation blocks α6β4-dependent VEGF mRNA translation.

Conclusions:

  • Integrin α6β4 regulates eIF4E activity through the Mnk1 kinase.
  • Mnk1 is a crucial mediator of α6β4 signaling in translational control.
  • Mnk1 represents a potential therapeutic target in cancers with high integrin α6β4 expression.

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