Related Experiment Video

Updated: Aug 27, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.0K

A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation

Marek M Drozdz1, Ashley S Doane2, Rached Alkallas3

  • 1Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10065, USA.

Cell Reports
|September 28, 2022
PubMed

Insights

Researchers discovered a nuclear cyclic AMP (cAMP) microdomain that inhibits YAP protein, a key cancer driver. This finding opens new therapeutic avenues for targeting cancer by modulating specific cAMP microdomains.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cyclic AMP (cAMP) signaling is compartmentalized into distinct microdomains.
  • The function of these cAMP microdomains in cancer cell biology remains largely unknown.
  • Understanding these microdomains is crucial for developing novel cancer therapies.

Purpose of the Study:

  • To investigate the role of specific cAMP microdomains in cancer.
  • To develop a genetic system for localized activation of cAMP signaling.
  • To identify novel mechanisms of cancer regulation by cAMP.

Main Methods:

  • Development of a tunable genetic system to activate cAMP signaling in specific cellular microdomains.
  • Utilizing cell biology techniques to study protein localization and signaling pathways.
  • Employing biochemical assays to analyze protein phosphorylation and stability.

Main Results:

  • Identification of a nuclear cAMP microdomain that suppresses tumor growth.
  • Demonstration that nuclear cAMP inhibits YAP (Yes-associated protein), a critical Hippo pathway effector, within the nucleus.
  • Elucidation of a LATS-dependent pathway leading to YAP phosphorylation at serine 397 and subsequent nuclear export, without affecting YAP stability.

Conclusions:

  • Nuclear cAMP signaling represents a novel tumor-suppressive mechanism by inhibiting nuclear YAP.
  • This mechanism is distinct from previously understood Hippo pathway regulation.
  • Targeting nuclear cAMP microdomains offers a promising, yet unexplored, therapeutic strategy for various cancers.
Keywords:
CP: Molecular biologyHippo pathwayPKAYAPcAMPnucleussACtumor suppression

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