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Updated: Jul 26, 2025

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
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Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

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CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling

Guillaume Serwe1,2, David Kachaner1, Jessica Gagnon1,2

  • 1Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.

Nature Communications
|June 15, 2023
PubMed

Insights

The scaffold protein CNK2 promotes cancer cell migration by linking the AXL receptor to ARF6 GTPase activation. Targeting CNK2 and SAMD12 may reduce cancer metastasis.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Signal transduction

Background:

  • Cell motility is crucial for invasive tumors, but the mechanisms linking external signals to motility machinery are not fully understood.
  • Understanding these pathways is key to developing anti-metastasis therapies.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which cancer cells achieve motility.
  • To identify novel targets for anti-metastasis therapies.

Main Methods:

  • Investigated the role of scaffold protein CNK2 in cancer cell migration.
  • Utilized biochemical assays, cell signaling analysis, and a mouse xenograft model.
  • Examined the interaction between AXL, CNK2, SAMD12, and GTPases ARF6, RAC1, and RHOA.

Main Results:

  • CNK2 couples the AXL receptor tyrosine kinase to ARF6 GTPase activation, promoting cancer cell migration.
  • AXL signaling recruits CNK2 to the plasma membrane, where it activates ARF6 via cytohesin ARF GEFs and SAMD12.
  • ARF6-GTP regulates cell motility by controlling RAC1 and RHOA GTPase activity.
  • Genetic deletion of CNK2 or SAMD12 significantly reduced metastasis in a mouse model.

Conclusions:

  • CNK2 and SAMD12 form a novel pro-motility pathway in cancer cells.
  • This pathway, involving AXL and ARF6, is critical for cancer cell migration and metastasis.
  • CNK2 and SAMD12 represent potential therapeutic targets for inhibiting cancer metastasis.

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