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Paralog Co-Targeting Identifies Selective Genetic Redundancies across Cancer Types

Gregory Gauthier-Coles1, Jason M Sheltzer1

  • 1Yale University School of Medicine, New Haven, Connecticut.

Cancer Discovery
|December 2, 2024
PubMed

Insights

Klingbeil and colleagues identified microtubule affinity-regulating kinases 2 and 3 as key regulators of the Hippo pathway. These kinases are potential therapeutic targets for YAP/TAZ-addicted cancers.

Area of Science:

  • Cell Biology
  • Molecular Oncology

Background:

  • The Hippo pathway is crucial for organ size control and tumor suppression.
  • YAP/TAZ are key downstream effectors of the Hippo pathway, often dysregulated in cancers.

Purpose of the Study:

  • To identify novel regulators of the Hippo pathway.
  • To explore potential therapeutic targets in YAP/TAZ-driven tumors.

Main Methods:

  • Employed a paralog co-targeting strategy.
  • Investigated the role of microtubule affinity-regulating kinases 2 and 3 (MARK2 and MARK3).

Main Results:

  • MARK2 and MARK3 function as redundant negative regulators of the Hippo pathway.
  • Inhibition of MARK2/MARK3 impacts Hippo pathway signaling.

Conclusions:

  • Microtubule affinity-regulating kinases 2 and 3 are critical for Hippo pathway homeostasis.
  • MARK2 and MARK3 represent actionable therapeutic targets for YAP/TAZ-addicted cancers.

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