Downstream targets of Fgfrl1 signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE32013 | GEO | 2012/03/16
SECONDARY ACCESSION(S): PRJNA147525
REPOSITORIES: GEO
Similar Datasets
Project description:Comparison of the gene expression profiles between normal and Fgfrl1 deficient kidneys 3 individual RNA preparations from 6-9 pooled normal kidneys each vs. 3 individual RNA preparations from 6-9 Fgfrl1-/- kidneys each
2012-03-16 | E-GEOD-32013 | biostudies-arrayexpress
Project description:Purpose: This study investigates the role of fibroblast growth factor receptor-like 1 (FGFRL1) in regulating androgen receptor (AR) and fibroblast growth factor receptor (FGFR) signaling pathways in advanced prostate cancer (PCa). Methodology: Clinical samples from two independent datasets (n=48 and n=492) were analyzed to compare the expression levels of FGFRL1, AR, and FGFR1 in PCa versus normal samples. Transient knockdown (KD) experiments using siRNA were conducted in LNCaP and 22RV1 PCa cell lines to reduce FGFRL1 expression by 60-80%. FGFR downstream signaling was assessed following R1881+FGF2 stimulation. Additionally, ChIP and RNA sequencing were used to explore FGFRL1's role in AR transcriptional binding and pathway analysis. Immunohistochemistry of FGFR1 and FGFRL1 staining of tumor microarrays (n=141) were quantified for their localization pattern. Immunofluorescence and subcellular protein fractionation followed by immunoblotting were used to quantify FGFR1, FGFRL1, AR and p-AR localization in the nucleus of PCa cell lines. Results The study found elevated levels of FGFRL1 and AR, and decreased FGFR1 expression in PCa samples compared to normal prostate samples. FGFRL1 KD led to significantly reduced AR binding to androgen response elements (AREs), despite the presence of synthetic androgen R1881. This reduction in AR activity was linked to decreased expression of AR-regulated proteins, such as CAMKK2 and pAKT. FGFRL1 KD also resulted in decreased AR phosphorylation at Ser81 and reduced nuclear translocation of FGFR1. Stimulation with R1881 and FGF2 increased FGFR downstream signaling upon FGFRL1 KD, as indicated by elevated pFRS2a and pERK1/2 levels. In the PCa patient cohort (n=141), FGFR1 and FGFRL1 localization patterns were correlated, with significant positive correlations between nuclear FGFRL1 and FGFR1. Significance This study provides novel insights into the role of FGFRL1 in modulating AR and FGFR signaling in PCa. By demonstrating that FGFRL1 KD affects AR binding and FGFR1 nuclear translocation, the research highlights potential targets for developing new combinatorial therapies for advanced PCa, particularly castration-resistant prostate cancer (CRPC). Understanding the interplay between FGFR and AR signaling may offer new strategies for overcoming resistance in PCa treatment.
2026-05-20 | GSE317205 | GEO
Project description:Purpose: This study investigates the role of fibroblast growth factor receptor-like 1 (FGFRL1) in regulating androgen receptor (AR) and fibroblast growth factor receptor (FGFR) signaling pathways in advanced prostate cancer (PCa). Methodology: Clinical samples from two independent datasets (n=48 and n=492) were analyzed to compare the expression levels of FGFRL1, AR, and FGFR1 in PCa versus normal samples. Transient knockdown (KD) experiments using siRNA were conducted in LNCaP and 22RV1 PCa cell lines to reduce FGFRL1 expression by 60-80%. FGFR downstream signaling was assessed following R1881+FGF2 stimulation. Additionally, ChIP and RNA sequencing were used to explore FGFRL1's role in AR transcriptional binding and pathway analysis. Immunohistochemistry of FGFR1 and FGFRL1 staining of tumor microarrays (n=141) were quantified for their localization pattern. Immunofluorescence and subcellular protein fractionation followed by immunoblotting were used to quantify FGFR1, FGFRL1, AR and p-AR localization in the nucleus of PCa cell lines. Results: The study found elevated levels of FGFRL1 and AR, and decreased FGFR1 expression in PCa samples compared to normal prostate samples. FGFRL1 KD led to significantly reduced AR binding to androgen response elements (AREs), despite the presence of synthetic androgen R1881. This reduction in AR activity was linked to decreased expression of AR-regulated proteins, such as CAMKK2 and pAKT. FGFRL1 KD also resulted in decreased AR phosphorylation at Ser81 and reduced nuclear translocation of FGFR1. Stimulation with R1881 and FGF2 increased FGFR downstream signaling upon FGFRL1 KD, as indicated by elevated pFRS2a and pERK1/2 levels. In the PCa patient cohort (n=141), FGFR1 and FGFRL1 localization patterns were correlated, with significant positive correlations between nuclear FGFRL1 and FGFR1. Significance: This study provides novel insights into the role of FGFRL1 in modulating AR and FGFR signaling in PCa. By demonstrating that FGFRL1 KD affects AR binding and FGFR1 nuclear translocation, the research highlights potential targets for developing new combinatorial therapies for advanced PCa, particularly castration-resistant prostate cancer (CRPC). Understanding the interplay between FGFR and AR signaling may offer new strategies for overcoming resistance in PCa treatment.
2026-05-20 | GSE319336 | GEO
Project description:Several genes were indicated as genes strongly affected by FGFRL1-deficiency, through expression profiling of a total of 25,000 genes in 2 wild type KYSE520 human oesphageal squamous cell carcinoma cells and 2 FGFRL1-deficient kYSE520 cells
2018-05-31 | GSE96956 | GEO
Project description:FGFRs regulate PCa development and progression, but the role of the recently found FGFR-like 1 (FGFRL1, FGFR5) remains unclear. The data consists of gene expression profiles of FGF13 and FGFRL1 knock-down PC3M prostate cancer cells compared to control cells.
2022-01-11 | GSE174148 | GEO
Project description:FGFRs regulate PCa development and progression, but the role of the recently found FGFR-like 1 (FGFRL1) remains unclear. The data consists of gene expression profiles of mouse subcutanous xenograft tumors generated of human PC3M prostate cancer cells with stable knockdown of FGFRL1 gene and of the control xenografts.
2022-01-11 | GSE174361 | GEO
Project description: Not available
| S-EPMC3303837 | biostudies-literature
Project description:Analysis of ovarian cancer cell lines after knockdown of FGFRL1 using SiRNA. To elucidate the signaling pathways that were significantly altered following the silencing of FGFRL1 expression, we performed global gene profiling experiments of the OVCAR8 and ES2 cells after knockdown of FGFRL1 using siRNA. We conducted pathway analysis with the differentially expressed genes using R in two OC cells.
2018-05-11 | GSE106549 | GEO
Project description:Despite 30 years of Hox gene study we have a remarkably limited knowledge of the downstream target genes that Hox transcription factors regulate to confer regional identity. Here, we have used a microarray approach to identify genes that function downstream of a single vertebrate Hox gene, zebrafish hoxb1a. This gene plays a critical and conserved role in vertebrate hindbrain development, conferring identity to hindbrain rhombomere 4. For example, zebrafish Hoxb1a, similar to mouse Hoxb1, is required for the migration of r4-derived facial branchiomotor neurons into the posterior hindbrain. We have screened microarrays carrying more than 16,000 expressed sequence tags (ESTs) for genes that are differentially regulated in normal versus Hoxb1a-deficient rhombomere 4 tissue. Using this approach, we have identified both positively and negatively regulated candidate Hoxb1a target genes. We have used in situ hybridization to validate twelve positively regulated Hoxb1a targets. These downstream targets are expressed in a variety of subdomains within r4, with one gene, a novel prickle homolog (pk1b), expressed specifically within the facial branchiomotor neurons. Using morpholino knock-down we show that the Hoxb1a target Pk1b is required for facial neuron migration, a single aspect of rhombomere 4 identity. Keywords: Comparison of normal and Hox-deficient tissue
2007-01-01 | GSE5199 | GEO
Project description:Notch signaling deficient kidney collecting ducts may serve as a useful resource to identify principal cell lineage and intercalated lineage specific factors since they develop a reduced number of principal cells and an increased number of intercalated cells compared with wild type kidney collecting ducts. We compared RNA from three E18.5 mouse kidneys per group: HoxB7Cre;RBPJf/-;Rosa+/Eyfp (Notch signaling deficient; mutant) versus RBPJf/f;Rosa+/Eyfp (wild type).
2017-02-27 | GSE68389 | GEO