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The antiproliferative effect of FGF2 in K-Ras-driven tumor cells involves modulation of rRNA and the nucleolus

Francisca N de Luna Vitorino1,2, Michaella J Levy3, Rosangela A Mansano Wailemann1

  • 1Laboratório de Ciclo Celular - Center of Toxins, Immune-Response and Cell Signalling - CeTICS, Instituto Butantan, São Paulo, SP 055503-900, Brazil.

Journal of Cell Science
|November 3, 2023
PubMed

Insights

Fibroblast Growth Factor 2 (FGF2) triggers antiproliferative effects by altering nucleolar proteins and ribosomal RNA (rRNA) transcription. These changes in the cell

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The nucleolus is a key cellular organelle sensitive to stress.
  • Fibroblast Growth Factor 2 (FGF2), typically a growth factor, exhibits antiproliferative and tumor-suppressive roles in certain contexts.
  • Understanding FGF2's impact on cellular regulation is crucial for cancer research.

Purpose of the Study:

  • To investigate how FGF2's antiproliferative effect modulates chromatin-, nucleolus-, and rDNA-associated proteins.
  • To elucidate the molecular mechanisms underlying FGF2-induced growth arrest.
  • To determine the role of rRNA expression in FGF2's antiproliferative function.

Main Methods:

  • Proteomic analysis of chromatin and nucleolar fractions.
  • Measurement of global transcriptional rates and nucleolus size.
  • Analysis of rDNA-associated proteins.
  • Assessment of rRNA processing and accumulation.
  • RNA Polymerase I (Pol I) inhibition experiments.

Main Results:

  • FGF2 stimulation altered proteins involved in transcription, rRNA expression, and chromatin remodeling.
  • A 24-hour FGF2 treatment increased global transcription, nucleolus area, and induced nucleolar disorganization.
  • Immature rRNA accumulation occurred due to increased rRNA transcription.
  • FGF2 stimulus interfered with transcription and rRNA processing, as evidenced by rDNA-associated protein analysis.
  • RNA Pol I inhibition partially rescued FGF2-induced growth arrest.

Conclusions:

  • Antiproliferative FGF2 stimulus induces significant transcriptional changes.
  • FGF2 modulates the nucleolus, the primary site of cellular transcription.
  • Altered rRNA expression plays a critical role in mediating FGF2's antiproliferative effects.
Keywords:
ChromatinFGF2NucleolusProteomicsTranscription

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