Fibroblast Growth Factor—14 Acts as Tumor Suppressor in Lung Adenocarcinomas
| Autor: | Rajkumar Savai, Mark Kriegsmann, Friedrich Grimminger, Michael Meister, Michael Thomas, David Brunn, Andreas Weigert, Werner Seeger, Stefan Günther, Kati Turkowski, Thomas Muley, Frederik Herzberg, Hauke Winter, Soni Savai Pullamsetti, Marc A Schneider |
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| Rok vydání: | 2020 |
| Předmět: |
Small interfering RNA
Epithelial-Mesenchymal Transition Lung Neoplasms xenograft model Down-Regulation Adenocarcinoma of Lung Kaplan-Meier Estimate Mice SCID lung cancer mesenchymal epithelial transition Biology Transfection Fibroblast growth factor Article Cohort Studies Extracellular matrix Mice Cell Movement Mice Inbred NOD Epidermal growth factor medicine Animals Humans Lung cancer lcsh:QH301-705.5 Cell Proliferation Tumor Suppressor Proteins RNA Cancer General Medicine lung adenocarcinoma medicine.disease fibroblast growth factor 14 Xenograft Model Antitumor Assays Fibroblast Growth Factors lcsh:Biology (General) A549 Cells Cancer research Adenocarcinoma Transcriptome |
| Zdroj: | Cells Volume 9 Issue 8 Cells, Vol 9, Iss 1755, p 1755 (2020) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9081755 |
| Popis: | Investigation of the molecular dynamics in lung cancer is crucial for the development of new treatment strategies. Fibroblast growth factor (FGF) 14 belongs to the FGF family, which might play a crucial role in cancer progression. We analyzed lung adenocarcinoma (LUAC) patients samples and found that FGF14 was downregulated, correlating with reduced survival and oncogenic mutation status. FGF14 overexpression in lung cancer cell lines resulted in decreased proliferation, colony formation, and migration, as well as increased expression of epithelial markers and a decreased expression of mesenchymal markers, indicating a mesenchymal to epithelial transition in vitro. We verified these findings using small interfering RNA against FGF14 and further confirmed the suppressive effect of FGF14 in a NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ immunodeficient xenograft tumor model. Moreover, FGF14 overexpressing tumor cell RNA sequencing data suggests that genes affected by FGF14 were related to the extracellular matrix, playing a role in proliferation and migration. Notably, newly identified FGF14 target genes, adenosine deaminase RNA specific B1 (ADARB1), collagen and calcium-binding epidermal growth factor domain-containing protein 1 (CCBE1), &alpha 1 chain of collagen XI (COL11A1), and mucin 16 (MUC16) expression was negatively correlated with overall survival when FGF14 was downregulated in LUAC. These findings led us to suggest that FGF14 regulates proliferation and migration in LUAC. |
| Databáze: | OpenAIRE |
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