Related Experiment Video

Updated: May 18, 2026

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
08:32

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

Published on: May 23, 2025

RNA interference screening identifies a novel role for autocrine fibroblast growth factor signaling in neuroblastoma

F Salm1, P Cwiek, A Ghosal

  • 1Department of Clinical Research, University of Bern, Bern, Switzerland.

Oncogene
|October 3, 2012
PubMed

Insights

Fibroblast growth factor receptor 2 (FGFR2) drives chemotherapy resistance in neuroblastoma (NB). Inhibiting FGFR2 sensitizes NB cells to cisplatin by downregulating anti-apoptotic proteins, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Chemotherapy resistance is a major challenge in treating high-risk neuroblastoma (NB), a common childhood cancer.
  • MYCN amplification is linked to poor prognosis in NB patients.

Purpose of the Study:

  • To identify genes contributing to cisplatin resistance in neuroblastoma using a kinome-wide RNA interference screen.
  • To investigate the role of fibroblast growth factor receptor 2 (FGFR2) in NB chemoresistance.

Main Methods:

  • Loss-of-function kinome-wide RNA interference screening was employed to identify sensitization genes.
  • Pharmacological inhibition of FGFR2 and gene silencing were used to assess its role in chemoresistance.
  • Western blotting and expression analysis were performed to elucidate the underlying mechanisms.

Main Results:

  • Fibroblast growth factor receptor 2 (FGFR2) was identified as a key determinant of cisplatin resistance in NB.
  • FGFR2 inhibition sensitized NB cells to cisplatin by downregulating anti-apoptotic proteins BCL2 and BCLXL.
  • FGFR2 activates protein kinase C-δ, leading to BCL2 expression and contributing to chemoresistance.
  • FGFR2 expression correlates with MYCN amplification and advanced disease stage in NB.

Conclusions:

  • FGFR2 plays a significant role in mediating chemoresistance in neuroblastoma.
  • Targeting FGFR2, potentially in combination with chemotherapy, represents a promising therapeutic strategy for NB treatment.

More Related Videos

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function08:04

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

Related Concept Videos

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...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...