Fibroblast growth factor receptor signalling dysregulation and targeting in breast cancer

Francavilla, Chiara; O'Brien, Ciara S

doi:10.1098/rsob.210373

Cited by 37 publications

(27 citation statements)

References 260 publications

(400 reference statements)

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“…Furthermore, the IGF1 signaling pathway has previously been shown to be critical for normal cell division and to be modulated in PABC ( Loddo et al, 2014 ). Targeted therapies have been developed for suppressing the post-partum pro-tumorigenic extracellular matrix via inhibition of PTGS2 ( O'Brien et al, 2011 ), and the potential benefit of targeting the FGF1 pathway in breast cancer has been considered ( Francavilla and O’Brien, 2022 ). On the other hand, CAV1 expression, which is down-regulated during tumorigenesis, has been shown to be suppressed during lactation ( Park et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Distinctive gene expression patterns in pregnancy-associated breast cancer

Wang

Peng

et al. 2022

Front. Genet.

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Pregnancy-associated breast cancer (PABC) is diagnosed during pregnancy or within 1 year postpartum, but the unique aspects of its etiology and pathogenesis have not been fully elucidated. This study aimed to ascertain the molecular mechanisms of PABC to facilitate diagnosis and therapeutic development. The Limma package was used to characterize the differentially expressed genes in PABC as compared to non-pregnancy-associated breast cancer (NPABC) and normal breast tissue. A total of 871 dysregulated genes were identified in the PABC versus NPABC groups and 917 in the PABC versus normal groups, with notable differences in the expression of MAGE and CXCL family genes. The dysregulated genes between the PABC and normal groups were mainly associated with signal transduction and immune response, while Kyoto Encyclopedia of Genes and Genomes analysis revealed that the dysregulated genes were enriched in immune-related pathways, including the major histocompatibility complex (MHC) class II protein complex, the type I interferon signaling pathway, regulation of α-β T-cell proliferation, and the T-cell apoptotic process. Through protein-protein interaction network construction, CD44 and BRCA1 were identified as prominent hub genes with differential expression in PABC versus NPABC. Furthermore, a cluster with eleven hub genes was identified in PABC versus normal adjacent tissues, of which the expression of EGFR, IGF1, PTGS2, FGF1, CAV1, and PLCB1 were verified to be differentially expressed in an independent cohort of PABC patients. Notably, IGF1, PTGS2, and FGF1 were demonstrated to be significantly related to patient prognosis. Our study reveals a distinctive gene expression pattern in PABC and suggests that IGF1, PTGS2, and FGF1 might serve as biomarkers for diagnosis and prognosis of PABC.

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Section: Discussionmentioning

confidence: 99%

Distinctive gene expression patterns in pregnancy-associated breast cancer

Wang

Peng

et al. 2022

Front. Genet.

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“…Research of FGFR1 and FGFR2 has increased over the past decade, and the relationship between them and various clinical characteristics has been eagerly sought by studying the detection of their expression in various malignant tumors using FGFR gene screening. Abnormal alteration or overexpression of FGFR1 and FGFR2 proteins has been found in oral SCC (15), esophageal SCC (16,17), lung cancer (18)(19)(20), breast cancer (21,22), and pancreatic cancer (23), and a clear association between high expression status and poor prognosis of patients has been observed. The application of FGFR inhibitors in the treatment of cholangiocarcinoma and urothelial malignancies has achieved initial results (24), while FGFR1 overexpression has been found in SCC of the head and neck (HNSCC) (25), and was associated with poor survival.…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical significance of FGFR1 and FGFR2 in laryngeal squamous cell carcinoma

Hu¹,

Zhang²

2022

Transl Cancer Res TCR

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Background: Fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor receptor 2 (FGFR2) may be of significance in the development of laryngeal squamous cell carcinoma (SCC) tissues.Examination of the expression results of these factors may offer new insights into treatment of the disease, such as genetic and histological targeted target therapy. Methods: We selected tissue from 30 cases of laryngeal SCC, 23 cases of adjacent normal mucosa, and 26 cases of benign laryngeal mucosal tissues from patients who received surgery at the Otolaryngology Department of the Affiliated Hospital of Chengde Medical College between September 2020 and January 2022. The laryngeal cancers included nine cases of supraglottic, 20 glottic (vocal cord), and one case of subglottic cancer, while all benign laryngeal mucosal lesions were obtained from vocal cord polyps. The expression of FGFR1 and FGFR2 was detected in 30 laryngeal cancers, 23 adjacent normal mucosa, and 26 vocal cord polyps by immunohistochemical technology [immunohistochemistry (IHC)], and the correlation analysis of their expression in laryngeal cancer was performed. P<0.05 was represented as significant.Results: The expression of FGFR1 and FGFR2 was significantly different in laryngeal SCC and the normal tissue >0.5 cm from the tumor margin (P<0.05), and between laryngeal SCC and vocal polyps (P<0.05).There was no difference in FGFR1 and FGFR2 expression (P>0.05) between normal mucosal margins and vocal cord polyp tissue, and no correlation between FGFR1 and FGFR2 in laryngeal SCC and sex, age, smoking history, alcohol consumption history, tumor diameter, tumor lymph node metastasis, tumor differentiation degree, and Tumor-Node-Metastasis (TNM) stage (P>0.05), A moderate positive correlation between FGFR1 expression and FGFR2 expression in laryngeal SCC was seen (Rs=0.499, P<0.01).Conclusions: FGFR1 and FGFR2 may participate in the occurrence of SCC of the throat: (I) positive FGFR1 and FGFR2 expressions are not associated with gender, age, smoking history, alcohol consumption history, tumor diameter, lymph node metastasis, degree of differentiation, or TNM stage. (II) FGFR2 increases successively with higher FGFR1 expression and with a positive correlation in laryngeal SCC.

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“… 11 , 38 Not only can HSPGs tether FGFs and enable them to function in an autocrine or paracrine way, but they also enhance FGFS signaling by forming FGF/FGFR/HSPG complexes. 39 In contrast, the endocrine FGF subclass ligands (FGF19, FGF21, and FGF23), with a weak affinity for HSPGs, utilize Klotho proteins as co‐receptors for binding to their respective FGFRs 37 , 40 (Figure 1B ). However, they exhibit a strong affinity for FGFR/Klotho complexes but a limited affinity for individual FGFRs or Klotho proteins.…”

Section: Fgf/fgfr Systemmentioning

confidence: 99%

FGF/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis

et al. 2023

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Background With millions of victims worldwide, multiple sclerosis is the second most common cause of disability among young adults. Although formidable advancements have been made in understanding the disease, the neurodegeneration associated with multiple sclerosis is only partially counteracted by current treatments, and effective therapy for progressive multiple sclerosis remains an unmet need. Therefore, new approaches are required to delay demyelination and the resulting disability and to restore neural function by promoting remyelination and neuronal repair. Aims The article reviews the latest literature in this field. Materials and methods The fibroblast growth factor (FGF) signaling pathway is a promising target in progressive multiple sclerosis. Discussion FGF signal transduction contributes to establishing the oligodendrocyte lineage, neural stem cell proliferation and differentiation, and myelination of the central nervous system. Furthermore, FGF signaling is implicated in the control of neuroinflammation. In recent years, interventions targeting FGF, and its receptor (FGFR) have been shown to ameliorate autoimmune encephalomyelitis symptoms in multiple sclerosis animal models moderately. Conclusion Here, we summarize the recent findings and investigate the role of FGF/FGFR signaling in the onset and progression, discuss the potential therapeutic advances, and offer fresh insights into managing multiple sclerosis.

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Fibroblast growth factor receptor signalling dysregulation and targeting in breast cancer

Cited by 37 publications

References 260 publications

Distinctive gene expression patterns in pregnancy-associated breast cancer

Distinctive gene expression patterns in pregnancy-associated breast cancer

Expression and clinical significance of FGFR1 and FGFR2 in laryngeal squamous cell carcinoma

FGF/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis

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