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Updated: May 13, 2025

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The Role of PHLDA3 in Cancer Progression and Its Potential as a Therapeutic Target

Walied A Kamel1,2, Jayaraman Krishnaraj1, Rieko Ohki1

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

Cancers
|April 14, 2025
PubMed

Insights

Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a tumor suppressor that inhibits cancer cell survival and signaling. This review highlights PHLDA3's role in suppressing cancer metastasis and invasion, identifying it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a p53-regulated tumor suppressor.
  • PHLDA3 inhibits AKT-mediated cell survival and oncogenic signaling pathways crucial for cancer progression.

Purpose of the Study:

  • To review the multifaceted roles of PHLDA3 in tumorigenesis, metastasis, and invasion.
  • To explore PHLDA3's regulatory mechanisms and clinical relevance in various cancer types.
  • To discuss PHLDA3's potential as a prognostic biomarker and therapeutic target.

Main Methods:

  • Literature review of studies on PHLDA3 function in cancer.
  • Analysis of PHLDA3 interactions with key signaling pathways (p53, PI3K/AKT, Wnt/β-catenin).
  • Examination of PHLDA3's role in epithelial-mesenchymal transition (EMT) and cellular invasion.

Main Results:

  • PHLDA3 is a critical regulator of metastatic pathways, influencing EMT and invasion.
  • PHLDA3 interacts with multiple signaling pathways involved in cancer progression.
  • PHLDA3 demonstrates potential as a prognostic biomarker and therapeutic target for advanced malignancies.

Conclusions:

  • PHLDA3 plays a significant role in suppressing cancer progression, particularly metastasis and invasion.
  • Understanding PHLDA3's complex interactions offers new therapeutic strategies for cancer treatment.
  • PHLDA3 represents a promising target for developing novel anti-cancer therapies.
Keywords:
AKT pathwayPHLDA3invasionmetastasisp53tumor progression

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