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NFATc3 Enhances DREAM Complex-Driven Transactivation

Jieun Ahn1, Yoojeong Seo1, Jinho Jang1

  • 1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Biorxiv : the Preprint Server for Biology
|February 6, 2026
PubMed

Insights

Nuclear Factor of Activated T cells (NFAT) transcription factors, specifically NFATc3, unexpectedly promote lung adenocarcinoma (LUAD) cell proliferation by activating DREAM target genes. Targeting the calcium-NFATc3 pathway offers a novel therapeutic strategy for LUAD.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Nuclear Factor of Activated T cells (NFAT) transcription factors regulate cellular processes but their role in tumor cells is unclear.
  • The DREAM complex controls cell quiescence and proliferation.
  • Lung adenocarcinoma (LUAD) cell proliferation mechanisms require further elucidation.

Purpose of the Study:

  • To investigate the role of NFAT transcription factors in LUAD.
  • To identify novel molecular targets for LUAD therapy.
  • To explore the interplay between calcium signaling, NFAT, and the DREAM complex in LUAD.

Main Methods:

  • Analysis of NFAT member expression in LUAD cells.
  • Investigating the requirement of NFATc3 for LUAD cell proliferation and DREAM target gene transactivation.
  • Chromatin immunoprecipitation to assess NFATc3 enrichment at DREAM target promoters.
  • Co-immunoprecipitation to study NFATc3 association with the DREAM complex.

Main Results:

  • NFATc3 was predominantly expressed in LUAD cells and essential for LUAD cell proliferation.
  • NFATc3 was required for DREAM target gene transactivation.
  • NFATc3 localized to DREAM target promoters and interacted with the DREAM complex, potentially via LIN9.

Conclusions:

  • NFATc3 plays an unexpected role in promoting DREAM target gene transactivation in LUAD.
  • The calcium-NFATc3 axis is a potential molecular target in LUAD.
  • DREAM complex activation enriches the calcium-NFATc3 pathway in LUAD.
Keywords:
CalciumDREAM complexLung AdenocarcinomaNFAT family proteinsNFATc3

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