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Updated: Jun 18, 2025

Development of Organoids from Mouse Pituitary as In Vitro Model to Explore Pituitary Stem Cell Biology
09:48

Development of Organoids from Mouse Pituitary as In Vitro Model to Explore Pituitary Stem Cell Biology

Published on: February 25, 2022

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Developmental pluripotency-associated 4 increases aggressiveness of pituitary neuroendocrine tumors by enhancing cell

Shaista Chaudhary1, Ujjal Das1, Shaima Jabbar2,1

  • 1The Endocrine Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.

Neuro-Oncology
|August 2, 2024
PubMed
Abstract

Insights

Developmental pluripotency-associated 4 (DPPA4) drives pituitary tumor stemness and aggressiveness by regulating WNT/β-CATENIN signaling. Targeting DPPA4 offers a potential therapeutic strategy for aggressive pituitary neuroendocrine tumors (PitNETs).

Area of Science:

  • Endocrinology
  • Cancer Biology
  • Molecular Oncology

Background:

  • Pituitary neuroendocrine tumors (PitNETs) are often aggressive and metastasize, with limited treatment options.
  • The molecular drivers of PitNET aggressiveness remain poorly understood.
  • Developmental pluripotency-associated 4 (DPPA4), a stem cell regulator, is overexpressed in some cancers but its role in PitNETs is unknown.

Purpose of the Study:

  • To investigate the role of DPPA4 in the aggressiveness of pituitary neuroendocrine tumors (PitNETs).
  • To elucidate the molecular mechanisms by which DPPA4 contributes to PitNET stemness and proliferation.

Main Methods:

  • Utilized both rat (prenatal-alcohol-exposed) and human pituitary tumor models.
  • Employed gene editing, ChIP assays, epigenetic studies, and receptor antagonism.
  • Assessed DPPA4 expression and its impact on cell proliferation, migration, and tumorigenic potential.

Main Results:

  • DPPA4 is overexpressed in aggressive PitNETs, correlating with increased cell stemness factors.
  • DPPA4 promotes PitNET cell proliferation, migration, and tumorigenesis by regulating WNT/β-CATENIN signaling.
  • Histone methyltransferase is involved in alcohol-induced activation of DPPA4.

Conclusions:

  • DPPA4 plays a significant role in pituitary tumor stemness and aggressiveness.
  • Targeting DPPA4 represents a potential therapeutic avenue for aggressive PitNETs.
  • Findings provide a preclinical basis for developing DPPA4-modulating therapies.
Keywords:
DPPA4WNT/β-CATENINhistone methyltransferasepituitary neuroendocrine tumorsprenatal alcohol

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