Related Experiment Video

Updated: Jun 8, 2025

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
07:26

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes

Published on: October 15, 2016

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Spatial organization of PI3K-PI(3,4,5)P3-AKT signaling by focal adhesions

Jing Wang1, Zhengyang An1, Zhongsheng Wu1

  • 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Molecular Cell
|November 2, 2024
PubMed

Insights

Focal adhesions organize phosphatidylinositol 3-kinase (PI3K)-AKT signaling in cancer cells, independent of growth factors. This spatial organization, regulated by focal adhesion kinase (FAK), offers new therapeutic targets.

Area of Science:

  • Cell Biology
  • Cancer Signaling
  • Molecular Mechanisms

Background:

  • The PI3K-AKT pathway is crucial for cell functions and frequently altered in cancer.
  • Spatial organization of PI3K-AKT signaling in cells is not well understood.

Purpose of the Study:

  • To identify subcellular locations and mechanisms of PI3K-AKT signaling activation in cancer cells.
  • To investigate the role of focal adhesions in organizing this pathway.

Main Methods:

  • Utilized human cancer cell lines with p110α mutations.
  • Investigated recruitment and activation of PI3K, PI(3,4,5)P3, and AKT1 at focal adhesions.
  • Examined the role of focal adhesion kinase (FAK) in regulating this cascade.

Main Results:

  • Identified focal adhesions as hubs for PI3K-AKT signaling activation under basal conditions.
  • Class IA PI3Ks and AKT1 are recruited and activated at focal adhesions.
  • FAK regulates the spatial activation of the PI3K-PI(3,4,5)P3-AKT cascade.
  • Combined inhibition of p110α and FAK showed potent anti-cancer effects.

Conclusions:

  • Focal adhesions compartmentalize PI3K-AKT signaling independently of growth factors.
  • Targeting both p110α and FAK presents a potential therapeutic strategy for cancer.
Keywords:
AKTFAKPI(3,4,5)P(3)class I PI3Kfocal adhesionlipid signalingsingle-molecule imaging

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