Fibroblast Growth Factors and their Emerging Cancer-Related Aspects

Khalid, Anibah; Javaid, Muhammad

doi:10.4172/1948-5956.1000413

Cited by 4 publications

(4 citation statements)

References 248 publications

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“…Fibroblast growth factor receptors (FGFR) comprise a group of four cell surface proteins that upon activation by fibroblast growth factors (FGFs) transmit signals from an extracellular environment, leading to cell proliferation, cell motility and the inhibition of apoptosis [ 1 ]. The malfunction in FGFR signaling (caused by mutations, gene rearrangements, gene multiplication and FGFR1 overexpression) has been observed in various malignancies such as breast, prostate and lung cancer [ 2 , 3 ]. Up to date, only small molecule FGFR inhibitors have been introduced to the market for the treatment of FGFR-dependent cancers [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

FGF2 Dual Warhead Conjugate with Monomethyl Auristatin E and α-Amanitin Displays a Cytotoxic Effect towards Cancer Cells Overproducing FGF Receptor 1

Świderska

Szlachcic

Opaliński

et al. 2018

IJMS

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In the rapidly developing field of targeted cancer therapy there is growing interest towards therapeutics combining two or more compounds to achieve synergistic action and minimize the chance of cancer resistance to treatment. We developed a fibroblast growth factor 2 (FGF2)-conjugate bearing two cytotoxic drugs with independent mode of action: α-amanitin and monomethyl auristatin E. Drugs are covalently attached to the targeting protein in a site-specific manner via maleimide-thiol conjugation and Cu(I)-catalyzed alkyne-azide cycloaddition. The dual warhead conjugate binds to FGF receptor 1 (FGFR1) and utilizes receptor-mediated endocytosis for selective internalization into cancer cells with FGFR1. The developed conjugate displays high cytotoxicity towards all tested FGFR1-positive cell lines. Most importantly, the improved cytotoxic effect of both drugs is observed for lung cancer cell line NCI-H446. The single drug-FGF2 conjugates have no impact on the viability of NCI-H446 cells, whereas the dual warhead-FGF2 conjugate selectively and efficiently kills these FGFR1 positive cancer cells. Due to the diversified mode of action the dual warhead-FGF2 conjugate may overcome the potential acquired resistance of FGFR1-overproducing cancer cells towards single cytotoxic drugs.

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Section: Introductionmentioning

confidence: 99%

FGF2 Dual Warhead Conjugate with Monomethyl Auristatin E and α-Amanitin Displays a Cytotoxic Effect towards Cancer Cells Overproducing FGF Receptor 1

Świderska

Szlachcic

Opaliński

et al. 2018

IJMS

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“…Interestingly, they have suggested the tumor suppressor role of FGF14 in colorectal cancer [29]. 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].…”

Section: Discussionmentioning

confidence: 99%

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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“…Fibroblast growth factors (FGFs) are proteinaceous substances that act in many biological, physiological, functional, and developmental processes. [ 1 ] FGF ligands in combination with fibroblast growth factor receptors (FGFRs, respective receptors) exhibit various controlled signaling pathways that bring about specific and regulated cellular responses. Any type of modification or mutation that causes changes in the FGF/FGFR signaling results in various types of abnormalities.…”

Section: Introductionmentioning

confidence: 99%

“…Any type of modification or mutation that causes changes in the FGF/FGFR signaling results in various types of abnormalities. [ 1 ] Point mutations, genetic alterations, and other related chromosomal aberrations that result in splice variants and altered FGFs have the potential to form cancer. [ 2 ] In the investigative protocols using the generation sequencing technique, conclusive results showed that a small amount (7% of cancers) is characterized by FGF–FGFR gene alterations.…”

Section: Introductionmentioning

confidence: 99%

Fibroblastic Growth Factor as a Diagnostic and Prognostic Marker in Odontogenic Cysts and Tumors: A Systematic Review

Rao¹,

Rosaian²,

Jawahar³

et al. 2021

Journal of Pharmacy and Bioallied Sciences

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Cellular signaling proteins maintain the basic activities of cell and communication, between the cells for normal growth and development and pathological situation as well. Fibroblast growth factor (FGF) and fibroblast growth factor receptors (FGFRs) have a comparatively huge part to play in the cellular communication processes. Human FGF has 22 members, 18 ligands, and 4 tyrosine kinase receptors for binding and is expressed in a wide range of cells. Any alteration in these factors would disrupt their normal function, leading to various abnormalities. The aim of this systematic analysis, is to understand the FGFs, the physiological and pathological role of FGF in oral diseases, and to predict the use of FGF in the predilection toward odontogenic cyst and tumors. This review helps confer the role of FGF in various physiological and pathological aspects in systemic diseases and analyzes its role in diagnosis and prognosis of odontogenic cysts and tumors.

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Fibroblast Growth Factors and their Emerging Cancer-Related Aspects

Cited by 4 publications

References 248 publications

FGF2 Dual Warhead Conjugate with Monomethyl Auristatin E and α-Amanitin Displays a Cytotoxic Effect towards Cancer Cells Overproducing FGF Receptor 1

FGF2 Dual Warhead Conjugate with Monomethyl Auristatin E and α-Amanitin Displays a Cytotoxic Effect towards Cancer Cells Overproducing FGF Receptor 1

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

Fibroblastic Growth Factor as a Diagnostic and Prognostic Marker in Odontogenic Cysts and Tumors: A Systematic Review

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