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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Published on: June 6, 2017

Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression

Jiyong Liang1, Joyce M Slingerland

  • 1Molecular and Cell Biology, Sunnybrook and Women's Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Cell Cycle (Georgetown, Tex.)
|July 10, 2003
PubMed

Insights

The PI3K/PKB (Akt) pathway promotes tumor progression by disrupting cell cycle control. Understanding its mechanisms offers new cancer therapeutic targets for improved treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as Akt) pathway is implicated in tumor progression.
  • Emerging evidence highlights its critical role in various cancers, making it an attractive therapeutic target.

Purpose of the Study:

  • To elucidate the mechanisms by which the PI3K/PKB (Akt) pathway drives tumor progression.
  • To identify novel substrates and regulatory networks involved in pathway-mediated cell cycle deregulation.

Main Methods:

  • Investigated the role of PKB in regulating cell cycle progression at the G1/S transition.
  • Identified p21Waf1/Cip1 and p27Kip1 as novel substrates of PKB.
  • Examined the pathway's involvement in the G2/M transition and DNA damage checkpoint control.

Main Results:

  • PKB (Akt) signaling inactivates GSK3-beta, increasing cyclin D1, and inhibits Forkhead transcription factors and tuberin (TSC2), reducing p27Kip1.
  • Hyperactivation of the PI3K pathway leads to cell cycle deregulation through novel PKB substrates p21Waf1/Cip1 and p27Kip1.
  • Constitutive PI3K pathway activation may impair DNA damage checkpoint control during the G2/M transition.

Conclusions:

  • The PI3K/PKB (Akt) pathway is a key regulator of cell cycle progression and a significant contributor to tumor development.
  • Targeting the PI3K/PKB (Akt) pathway holds promise for novel cancer therapies by addressing cell cycle deregulation and DNA damage response.

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