FGF2 Antiproliferative Stimulation Induces Proteomic Dynamic Changes and High Expression of FOSB and JUNB in

Francisca Nathalia de Luna Vitorino1, Fabio Montoni1, Jaqueline Neves Moreno1

  • 1Laboratório Especial de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signaling - CeTICS, Instituto Butantan, São Paulo, SP, 05503-900, Brazil.

Proteomics
|July 24, 2018
PubMed

Insights

Fibroblast growth factor 2 (FGF2) can halt cell proliferation by altering cellular processes. This study reveals FGF2 impacts metabolism and DNA replication via transcription factors FOSB and JUNB, with FOSB delaying S-phase progression.

Area of Science:

  • Molecular Biology
  • Proteomics
  • Cancer Research

Background:

  • Fibroblast growth factor 2 (FGF2) is known to promote cell proliferation but can also induce cell cycle arrest.
  • The molecular mechanisms underlying FGF2's antiproliferative effects remain incompletely understood.
  • Investigating early proteomic changes offers insight into FGF2-induced growth inhibition.

Purpose of the Study:

  • To elucidate the early systemic proteomic differences induced by FGF2 in a K-Ras-driven mouse tumor cell line.
  • To identify key molecular players and pathways regulated by FGF2 during cell cycle arrest.
  • To investigate the role of transcription factors FOSB and JUNB in FGF2's antiproliferative effects.

Main Methods:

  • Quantitative proteomics approach to analyze protein expression changes.
  • Analysis of over 2900 proteins in a K-Ras-driven mouse tumor cell line (Y1) upon FGF2 stimulation.
  • Transcription regulatory network analysis and gene knockdown experiments in Y1, SK-N-MC, and UM-UC-3 cell lines.

Main Results:

  • FGF2 stimulation enriched proteins associated with metabolism, RNA processing, replication, and transcription.
  • FGF2 delayed abundance changes for proteins involved in DNA replication and carbohydrate metabolism.
  • FOSB and JUNB were identified as master regulators; FOSB knockdown rescued S-phase progression delay but not overall growth arrest.

Conclusions:

  • FGF2 induces complex proteomic changes impacting metabolism and cell cycle regulation.
  • FOSB plays a critical role in mediating the S-phase progression delay induced by FGF2.
  • Understanding these FGF2-driven pathways provides insights into potential therapeutic strategies for FGF2-responsive cancers.

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