Silencing or inhibition of mutant FGFR3 in bladder cancer cell lines is associated with decreased malignant potential, confirming its important driver role in UC.
Recent precision medicine has shown that mutations in BC are frequently observed in FGFR3, RAS and PIK3CA genes, all of which correlate with RAS signaling networks.
PATIENT SUMMARY: We propose that APOBEC-mediated mutagenesis can generate clinically relevant driver mutations even within suboptimal motifs, such as in the case of FGFR3S249C, one of the most common mutations in bladder cancer.
The aim of this paper was to report the most pivotal trials that evaluated different families of targeted therapy in the treatment of BC, according to their biomarkers (FGFR3, EGFR, HER2, VEGF and PI3K/AKT/mTOR).
Here we show that HDAC6 loss or inhibition reduces FGFR3 accumulation in cells made tumorigenic by ectopic expression of a mutant activated version of FGFR3 together with the MYC oncoprotein and in a bladder cancer cell line whose tumorigenicity is dependent on expression of a translocated version of FGFR3.
Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1.
The present study examined the utility of fibroblast growth factor receptor 3 (<i>FGFR3</i>) mutation status and gene expression as a prognostic marker in primary pT1 bladder cancer (BC).
The GSE41035 dataset downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) between bladder cancer cell line RT112 with or without depletion of FGFR3, and gene ontology enrichment analysis was performed.
We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients.
Our findings are consistent with the results of the TCGA data set for the "squamous-like" subtype of bladder cancer (n = 85), which revealed reduced overall expression of FGFR1 and FGFR2 in tumors compared to normal tissue, while expression of FGFR3 remained high.
In non-invasive BC, these mutations were related to high risk and grade (p<0.0001) as well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05).
Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer.
Knockdown of endogenous FGFR3 impaired the activity of daidzein against bladder cancer, which suggested that the effect of daidzein was mainly mediated by FGFR3 pathway.