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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas

Bhuvanesh Singh1, Pabbathi G Reddy, Andy Goberdhan

  • 1Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. singhb@mskcc.org

Genes & Development
|April 18, 2002
PubMed

Insights

The p53 and PI3K/AKT pathways interact to control cell fate. In upper aerodigestive tract cancers, p53 inhibits PIK3CA, a key oncogene, promoting apoptosis independent of PTEN.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The p53 and PI3K/AKT pathways are critical regulators of cell death and survival.
  • In normal cells, p53 transcriptionally regulates PTEN, which suppresses AKT activity and promotes apoptosis.
  • The interplay between these pathways in cancer, particularly in upper aerodigestive tract (UADT) carcinomas, remains unclear.

Purpose of the Study:

  • To investigate the relationship between the p53 and PI3K/AKT pathways in UADT carcinomas.
  • To determine the role of PIK3CA as an oncogene in these cancers.
  • To elucidate the mechanisms by which p53 influences cell survival in the context of PI3K/AKT pathway activation.

Main Methods:

  • Analysis of PIK3CA as an oncogene in UADT carcinomas.
  • Investigation of the mutual exclusivity between PIK3CA amplification and p53 mutation.
  • Examination of p53's transcriptional regulation of PIK3CA.
  • Assessment of PTEN expression and its role in p53-mediated apoptosis.

Main Results:

  • PIK3CA is identified as an oncogene in UADT carcinomas, with amplification and p53 mutation being mutually exclusive events.
  • p53 induction inhibits PIK3CA transcription, promoting cell death independently of PTEN.
  • Constitutive PIK3CA activation confers resistance to p53-induced apoptosis in PTEN-deficient cells.

Conclusions:

  • p53 regulates cell survival by transcriptionally inhibiting the PI3K/AKT pathway, independent of PTEN, in epithelial tumors.
  • This p53-mediated inhibition of PI3K/AKT signaling is essential for apoptosis in malignant cells.
  • Aberrant activation of either p53 or PIK3CA can drive tumorigenesis in UADT carcinomas.

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