Fibroblast Growth Factor—14 Acts as Tumor Suppressor in Lung Adenocarcinomas

Turkowski, Kati; Herzberg, Frederik; Günther, Stefan; Brunn, David; Weigert, Andreas; Meister, Michael; Muley, Thomas; Kriegsmann, Mark; Schneider, Marc A.; Winter, Hauke; Thomas, Michael; Grimminger, Friedrich; Seeger, Werner; Savai, Rajkumar

doi:10.3390/cells9081755

Cited by 17 publications

(12 citation statements)

References 56 publications

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“…Of note, a recent study reported that FGF12 (the homologue of FGF14 [30]) have a malignancy-inhibitor effect on pancreatic cancer cell lines [31]. Two most recent studies reported that FGF14 overexpression leads to tumor suppressive effects in lung adenocarcinoma and nasopharyngeal carcinoma [32,33]. In line with the previous in-vitro…”

Section: Discussionsupporting

confidence: 74%

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

2021

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Background Fibroblast (FGFs) and insulin (IGF) growth factor pathways are among 10 most recurrently altered genomic pathways in pancreatic ductal adenocarcinoma (PDAC). However, the prognostic and therapeutic relevance of FGF and IGF pathways in PDAC is largely unknown. Methods We investigated the relationship between fibroblast and insulin pathway gene expression and clinicopathological features in three independent transcriptomic cohorts of 532 PDAC patients. Furthermore, we have examined the coexpressed genes specific to the prognostic marker identified from these cohorts. Statistical tests including Fisher-exact\Chi-square, Kaplan–Meier, Pearson Correlation and cox regression analyses were performed. Additionally, pathway analysis of gene-specific co-expressed genes was also performed. Results The dysregulation of six genes including FGF9, FGF14, FGFR1, FGFR4, IGF2BP2 and IGF2BP3 were significantly associated with different clinical characteristics (including grade, stage, recurrence and nodes) in PDAC cohorts. 11 genes (including FGF9, FGF13, FGF14, FGF17, FGFR1, FGFRL1, FGFBP3, IGFBP3, IGF2BP2, IGF2BP3 and IGFBPL1) showed association with overall survival in different PDAC cohorts. Interestingly, overexpression of FGF14 was found associated with better overall survival (OS) in all three cohorts. Of note, multivariate analysis also revealed FGF14 as an independent prognostic marker for better OS in all three cohorts. Furthermore, FMN2 and PGR were among the top genes that correlated with FGF14 in all 3 cohorts. Of note, overexpression of FMN2 and PGR was found significantly associated with good overall survival in PDAC patients, suggesting FMN2 and PGR can also act as potential markers for the prediction of prognosis in PDAC patients. Conclusion FGF14 may define a distinct subset of PDAC patients with better prognosis. Moreover, FGF14-based sub-classification of PDAC suggests that FMN2 and PGR can be employed as good prognostic markers in PDAC and this classification may lead to new therapeutic approaches.

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Section: Discussionsupporting

confidence: 74%

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

2021

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“…Another factor that regulates COL11A1 expression is Fibroblast Growth Factor-14 (FGF-14). FGF-14 is downregulated in lung adenocarcinoma patient samples [ 61 ], and the overexpression of FGF-14 in the lung adenocarcinoma cell line A549 results in downregulation of COL11A1 expression.…”

Section: Col11a1 Signalingmentioning

confidence: 99%

Collagen Type XI Alpha 1 (COL11A1): A Novel Biomarker and a Key Player in Cancer

Nallanthighal

Heiserman

Cheon

2021

Cancers

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Collagen type XI alpha 1 (COL11A1), one of the three alpha chains of type XI collagen, is crucial for bone development and collagen fiber assembly. Interestingly, COL11A1 expression is increased in several cancers and high levels of COL11A1 are often associated with poor survival, chemoresistance, and recurrence. This review will discuss the recent discoveries in the biological functions of COL11A1 in cancer. COL11A1 is predominantly expressed and secreted by a subset of cancer-associated fibroblasts, modulating tumor-stroma interaction and mechanical properties of extracellular matrix. COL11A1 also promotes cancer cell migration, metastasis, and therapy resistance by activating pro-survival pathways and modulating tumor metabolic phenotype. Several inhibitors that are currently being tested in clinical trials for cancer or used in clinic for other diseases, can be potentially used to target COL11A1 signaling. Collectively, this review underscores the role of COL11A1 as a promising biomarker and a key player in cancer.

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“…Furthermore, in breast cancer patients receiving radiochemotherapy (5-fluorouracil, vinorelbine, radiotherapy), FGFR1 expression correlated with good response to treatment, whereas FGFR1-negative cancers showed resistance to this treatment [ 252 ]. Additionally, the reduced FGF14 level was correlated with poor survival and oncogenic mutation status (e.g., KRAS, EGFR) in lung adenocarcinoma (LUAC) patients [ 253 ]. Overexpression of FGF14 in NSCLC LUAC cell line (A549) resulted in decreased proliferation, colony formation and migration, and enhanced mesenchymal to epithelial transition, indicating that FGF14 reduces the invasiveness of lung cancer cells in vitro while ablation of FGF14 in these cells reversed the above changes, supporting its suppressive role in lung cancer progression.…”

Section: Enhancement Of Chemotherapy By Fgfs/fgfrs Actionmentioning

confidence: 99%

FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance

Szymczyk

Sluzalska

Materla

et al. 2021

Cancers

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Increased expression of both FGF proteins and their receptors observed in many cancers is often associated with the development of chemoresistance, limiting the effectiveness of currently used anti-cancer therapies. Malfunctioning of the FGF/FGFR axis in cancer cells generates a number of molecular mechanisms that may affect the sensitivity of tumors to the applied drugs. Of key importance is the deregulation of cell signaling, which can lead to increased cell proliferation, survival, and motility, and ultimately to malignancy. Signaling pathways activated by FGFRs inhibit apoptosis, reducing the cytotoxic effect of some anti-cancer drugs. FGFRs-dependent signaling may also initiate angiogenesis and EMT, which facilitates metastasis and also correlates with drug resistance. Therefore, treatment strategies based on FGF/FGFR inhibition (using receptor inhibitors, ligand traps, monoclonal antibodies, or microRNAs) appear to be extremely promising. However, this approach may lead to further development of resistance through acquisition of specific mutations, metabolism switching, and molecular cross-talks. This review brings together information on the mechanisms underlying the involvement of the FGF/FGFR axis in the generation of drug resistance in cancer and highlights the need for further research to overcome this serious problem with novel therapeutic strategies.

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Fibroblast Growth Factor—14 Acts as Tumor Suppressor in Lung Adenocarcinomas

Cited by 17 publications

References 56 publications

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

Genomic relevance of FGF14 and associated genes on the prognosis of pancreatic cancer

Collagen Type XI Alpha 1 (COL11A1): A Novel Biomarker and a Key Player in Cancer

FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance

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