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Fibroblast growth factor signals drive the metastatic behavior in small cell lung cancer

Ernhofer, Büsra ; Solta, Anna ; Sinner, Julia ; Megyesfalvi, Zsolt ; Deloria, Abigail J. ; Boettiger, Kristiina ; Glatt, Lisa ; Horvath, Lilla ; Sturtzel, Caterina and Wenninger-Weinzierl, Andrea , et al. (2026) In British Journal of Cancer 134(4). p.543-554
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... (More)

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. (Figure presented.)

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
134
issue
4
pages
12 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:105024821137
  • pmid:41390896
ISSN
0007-0920
DOI
10.1038/s41416-025-03276-y
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
077853d3-747e-4375-b2da-2d64d30f52d7
date added to LUP
2026-03-03 16:08:51
date last changed
2026-03-31 22:28:39
@article{077853d3-747e-4375-b2da-2d64d30f52d7,
  abstract     = {{<p>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. (Figure presented.)</p>}},
  author       = {{Ernhofer, Büsra and Solta, Anna and Sinner, Julia and Megyesfalvi, Zsolt and Deloria, Abigail J. and Boettiger, Kristiina and Glatt, Lisa and Horvath, Lilla and Sturtzel, Caterina and Wenninger-Weinzierl, Andrea and Distel, Martin and Grusch, Michael and Szeitz, Beata and Rezeli, Melinda and Aigner, Clemens and Dome, Balazs and Schelch, Karin}},
  issn         = {{0007-0920}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{4}},
  pages        = {{543--554}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{Fibroblast growth factor signals drive the metastatic behavior in small cell lung cancer}},
  url          = {{http://dx.doi.org/10.1038/s41416-025-03276-y}},
  doi          = {{10.1038/s41416-025-03276-y}},
  volume       = {{134}},
  year         = {{2026}},
}