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Updated: Dec 18, 2025

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

Published on: August 4, 2019

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p53-PHLDA3-Akt Network: The Key Regulators of Neuroendocrine Tumorigenesis

Yu Chen1, Rieko Ohki1

  • 1Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.

International Journal of Molecular Sciences
|June 12, 2020
PubMed

Insights

The tumor suppressor PHLDA3, a target of p53, inhibits pancreatic neuroendocrine tumor growth by repressing Akt. Loss of PHLDA3 function correlates with poor prognosis and may guide NET therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • p53 is a crucial tumor suppressor gene regulating cell proliferation and apoptosis.
  • Akt signaling pathway is frequently dysregulated in various cancers, including neuroendocrine tumors (NETs).

Purpose of the Study:

  • To investigate the role of PHLDA3 as a p53 target gene in pancreatic neuroendocrine tumors (PanNETs).
  • To elucidate the functional relationship between the p53-PHLDA3 axis and the Akt pathway in NET development.

Main Methods:

  • Identification of PHLDA3 as a p53 target gene.
  • Analysis of PHLDA3 inactivation (LOH, methylation) in human PanNETs.
  • Assessment of PHLDA3 function in PHLDA3-deficient mouse models.

Main Results:

  • PHLDA3 acts as a tumor suppressor in PanNETs and inhibits Akt signaling.
  • PHLDA3 is frequently inactivated in human PanNETs, with LOH correlating to tumor progression and poor prognosis.
  • PHLDA3 deficiency in mice leads to abnormal pancreatic islet cell proliferation and resistance to apoptosis.

Conclusions:

  • The p53-PHLDA3 pathway is a critical suppressor of NETs.
  • Loss of PHLDA3 function may serve as a prognostic marker for NET patients.
  • Targeting the PHLDA3-Akt pathway offers potential therapeutic strategies for NETs.
Keywords:
AktPHLDA3neuroendocrine tumorp53

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