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The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling

Yangyang Fu1, Shishun Huang2, Rulu Pan3

  • 1Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Communications Biology
|February 5, 2025
PubMed

Insights

Phosphodiesterase 4D interacting protein (PDE4DIP) is overexpressed in non-small cell lung cancer (NSCLC), driving tumor growth. Inhibiting PDE4DIP triggers cancer cell death and offers a potential therapeutic strategy for NSCLC patients.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Phosphodiesterase 4D interacting protein (PDE4DIP) is a Golgi/centrosome-associated protein involved in microtubule dynamics and Golgi structure.
  • The role of PDE4DIP in human cancer, particularly non-small cell lung cancer (NSCLC), is largely unexplored.

Purpose of the Study:

  • To investigate the biological role of PDE4DIP in NSCLC.
  • To determine the prognostic significance of PDE4DIP expression in lung cancer patients.
  • To elucidate the molecular mechanisms underlying PDE4DIP's function in NSCLC growth and survival.

Main Methods:

  • Analysis of PDE4DIP expression in NSCLC tissues.
  • In vitro and in vivo studies involving PDE4DIP knockdown in NSCLC cells.
  • Investigation of apoptosis, cell cycle, and signaling pathways (PKA/CREB) following PDE4DIP depletion.
  • Assessment of PDE4DIP's interaction with A-kinase anchoring proteins 9 (AKAP9) and its effect on Protein kinase A (PKA) RIIα localization and stability.

Main Results:

  • PDE4DIP is overexpressed in NSCLC tissues and associated with poor prognosis.
  • PDE4DIP knockdown inhibits NSCLC cell proliferation, tumorigenicity, and induces apoptosis and cell cycle arrest.
  • PDE4DIP activates the PKA/CREB signaling pathway by stabilizing Golgi-localized PKA RIIα via interaction with AKAP9.
  • PDE4DIP depletion leads to PKA RIIα mislocalization and degradation, impairing PKA signaling.

Conclusions:

  • PDE4DIP plays a significant role in NSCLC progression.
  • The PDE4DIP-AKAP9 complex regulates PKA signaling, impacting NSCLC growth.
  • PDE4DIP represents a potential therapeutic target for NSCLC.

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