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A diphtheria toxin/fibroblast growth factor 6 mitotoxin selectively kills fibroblast growth factor
M Batoz1, P M Coll Fresno, S Pizette
1Laboratoire d'Oncologie Moléculaire, Unité 119 de I'INSERM, Marseille, France.
Abstract:
The fibroblast growth factors (FGFs) constitute a family of nine polypeptides implicated in a number of physiological and pathological processes. They bind to at least three types of cell surface molecules, including low and high affinity receptor families. The role of FGFs and their receptors in human tumorigenesis has been suspected but not formally proven. FGF6 is an oncogene encoding a precursor protein of 208 amino acids that has been shown to bind to FGF receptors. Its normal function has not been identified, but its restricted pattern of expression suggests a role in muscle development or function. We have constructed, produced, and purified a diphtheria toxin/FGF6 mitotoxin that selectively kills FGF receptor-expressing cells. Interestingly, at least two cell lines that normally respond to FGF6 have been found resistant to DT/FGF6, suggesting that FGF6 acts on these cells through a transduction pathway that does not involve FGF receptor.
Insights
Fibroblast growth factors (FGFs) are involved in cell processes. A new diphtheria toxin/FGF6 mitotoxin selectively targets FGF receptor-expressing cells, revealing alternative FGF6 signaling pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Fibroblast growth factors (FGFs) are a family of nine polypeptides involved in various physiological and pathological processes.
- FGFs bind to cell surface molecules, including low and high affinity receptors.
- The role of FGFs and their receptors in human tumorigenesis is suspected but not definitively proven.
Purpose of the Study:
- To investigate the role of FGF6 in cellular processes and tumorigenesis.
- To develop a tool for selectively targeting FGF receptor-expressing cells.
- To explore alternative signaling pathways for FGF6.
Main Methods:
- Construction, production, and purification of a diphtheria toxin/FGF6 mitotoxin (DT/FGF6).
- Testing the selective toxicity of DT/FGF6 on FGF receptor-expressing cells.
- Analyzing the response of cell lines to FGF6 and DT/FGF6.
Main Results:
- DT/FGF6 selectively kills FGF receptor-expressing cells.
- Certain cell lines that normally respond to FGF6 were resistant to DT/FGF6.
- This resistance suggests an FGF receptor-independent transduction pathway for FGF6.
Conclusions:
- A novel DT/FGF6 mitotoxin can selectively eliminate FGF receptor-expressing cells.
- FGF6 may utilize alternative signaling pathways independent of its canonical receptors.
- Further research is warranted to elucidate these alternative pathways and their implications in cancer.