PUBLICATION
Fibroblast growth factor signals drive the metastatic behavior in small cell lung cancer
- Authors
- Ernhofer, B., Solta, A., Sinner, J., Megyesfalvi, Z., Deloria, A.J., Boettiger, K., Glatt, L., Horvath, L., Sturtzel, C., Wenninger-Weinzierl, A., Distel, M., Grusch, M., Szeitz, B., Rezeli, M., Aigner, C., Dome, B., Schelch, K.
- ID
- ZDB-PUB-251214-10
- Date
- 2025
- Source
- British journal of cancer : (Journal)
- Registered Authors
- Distel, Martin, Sturtzel, Caterina, Wenninger-Weinzierl, Andrea
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Movement
- Coculture Techniques
- Fibroblast Growth Factor 2*/metabolism
- Fibroblast Growth Factors*/metabolism
- Humans
- Lung Neoplasms*/genetics
- Lung Neoplasms*/metabolism
- Lung Neoplasms*/pathology
- Neoplasm Invasiveness
- Neoplasm Metastasis
- Proteomics/methods
- Signal Transduction
- Small Cell Lung Carcinoma*/genetics
- Small Cell Lung Carcinoma*/metabolism
- Small Cell Lung Carcinoma*/pathology
- Spheroids, Cellular/pathology
- Transcription Factors
- YAP-Signaling Proteins
- Zebrafish
- PubMed
- 41390896 Full text @ Br. J. Cancer
Citation
Ernhofer, B., Solta, A., Sinner, J., Megyesfalvi, Z., Deloria, A.J., Boettiger, K., Glatt, L., Horvath, L., Sturtzel, C., Wenninger-Weinzierl, A., Distel, M., Grusch, M., Szeitz, B., Rezeli, M., Aigner, C., Dome, B., Schelch, K. (2025) Fibroblast growth factor signals drive the metastatic behavior in small cell lung cancer. British journal of cancer. :.
Abstract
Background Early metastatic spread represents a challenge in fighting small cell lung cancer (SCLC). The molecular mechanisms underlying metastatic dissemination remain unclear in this devastating disease.
Methods Invasive traits were investigated in 13 SCLC cell lines using 3D-spheroid formation, sprouting assays, co-cultures and a zebrafish xenograft model. Proteomic analysis was performed to unravel metastatic drivers, which were validated by qPCR, growth factor arrays and specific inhibitors.
Results Overall, 8 cell lines formed spheroids, and half of these displayed invasive sprouting in collagen. The 'sprouter' SCLC cells, which all had a YAP1-dominant subtype, showed increased migration in zebrafish larvae and penetrated endothelial cell monolayers to a higher extent, thereby mimicking intra- and extravasation. Proteomics revealed differences in adhesion properties, oncogenic pathways and receptor tyrosine kinase signalling. Sprouter cells showed higher expression levels of mesenchymal cell state markers. Stimulation with fibroblast growth factor 2 (FGF2) further induced invasive sprouting, while blocking the FGF/R axis resulted in a significant reduction of sprouting in vitro and in vivo.
Conclusion The FGF/R axis is a key driver of SCLC metastatic spread in the YAP1-dominant subtype. These data might facilitate the development of potential future therapies targeting FGF/R signalling to prevent SCLC progression and metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping