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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
PI 3-kinase, Akt and cell survival
1Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. downward@cancer.org.uk
Seminars in Cell & Developmental Biology
|June 24, 2004
Summary
Phosphoinositide 3-OH kinase (PI 3-kinase) signaling promotes cell survival by activating Akt, which counters apoptosis. This pathway is often dysregulated in cancer cells, contributing to their resistance to cell death.
Area of Science:
- Cellular Biology
- Molecular Oncology
- Biochemistry
Background:
- Phosphoinositide 3-OH kinase (PI 3-kinase) is crucial for cell survival signals, enabling cells to resist apoptosis.
- Elevated PI 3-kinase activity is common in tumor cells due to PTEN loss, Ras activation, or autocrine growth factors, conferring apoptosis resistance.
Purpose of the Study:
- To elucidate the mechanisms of PI 3-kinase-mediated survival signaling.
- To understand the role of Akt in mediating PI 3-kinase survival effects.
- To explore novel connections between Akt's metabolic functions and cell survival.
Main Methods:
- Investigating the role of Akt as the principal mediator of PI 3-kinase survival signaling.
- Analyzing Akt's direct effects on apoptotic machinery, including targeting BAD.
- Examining Akt's influence on transcriptional responses via Forkhead factors and p53 family activity.
Main Results:
- Akt, activated by PI 3-kinase, directly impacts apoptosis regulators like BAD.
- Akt modulates the transcriptional response to apoptotic stimuli by affecting Forkhead factors.
- Akt influences the activity of the p53 family, contributing to cell survival.
- New links between Akt's metabolic actions and survival control have been identified.
Conclusions:
- PI 3-kinase signaling, primarily through Akt, is a key determinant of cell survival.
- Dysregulation of this pathway in cancer contributes to apoptosis resistance.
- Akt's multifaceted roles, including direct and indirect mechanisms and metabolic links, underscore its importance in cell survival.
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