Related Experiment Video

Updated: Jul 3, 2026

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

Fibroblast growth factor 2 restrains Ras-driven proliferation of malignant cells by triggering RhoA-mediated

Erico T Costa1, Fábio L Forti, Tatiana G F Matos

  • 1Departmento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.

Cancer Research
|August 5, 2008
PubMed

Insights

Fibroblast growth factor 2 (FGF2) induces senescence and inhibits proliferation in Ras-dependent malignant cells, not in normal cells. This unexpected finding challenges FGF2

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Fibroblast growth factor 2 (FGF2) is traditionally viewed as an oncogenic factor.
  • Emerging evidence suggests a more complex role for FGF2 in cancer development.
  • Understanding FGF2's precise function in malignant cells is crucial for cancer therapy.

Purpose of the Study:

  • To investigate the role of exogenous recombinant FGF2 in Ras-dependent malignant cells.
  • To determine the mechanisms by which FGF2 affects cell proliferation and tumor onset.
  • To explore the potential of targeting FGF2 or its downstream pathways in cancer treatment.

Main Methods:

  • Treatment of K-Ras-dependent Y1 adrenocortical cells and H-Ras V12-transformed BALB-3T3 fibroblasts with FGF2.
  • Assessment of cell proliferation, cell cycle, senescence (beta-galactosidase assay), apoptosis, and necrosis.
  • Inhibition studies using tyrosine kinase inhibitors (PD173074) and dominant-negative mutants (RasN17, RhoA-N19).
  • Tumorigenicity assays in nude and immunocompetent mice.

Main Results:

  • FGF2 irreversibly inhibited proliferation and induced senescence in Ras-dependent malignant cells, but not in normal cell lines.
  • FGF2 blocked the cell cycle and tumor onset in vivo without inducing apoptosis or necrosis.
  • Inhibition of Ras or RhoA signaling pathways conferred resistance to FGF2-induced senescence.
  • Attempts to develop FGF2-resistant cells revealed rare clones that lost the Ras oncogene and became FGF2-dependent.

Conclusions:

  • In Ras-dependent malignant cells, FGF2 triggers a senescence-like process mediated by RhoA-GTP.
  • FGF2 acts as a negative selective pressure against Ras-dependent malignant cells.
  • These findings challenge the oncogenic role of FGF2 and suggest potential therapeutic applications.

More Related Videos

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery07:20

A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery

Published on: February 28, 2020

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...