Fibroblast growth factor receptor 4 (FGFR4) is known to induce cancer cell proliferation, invasion, and anti-apoptosis through activation of the RAS / RAF / ERK and PI3K / pathways AKT, also known as the molecular basis primary carcinogenesis of colon cancer associated with EGFR signaling. However, the interaction of FGFR4 and EGFR signal with respect to the development of colon cancer is not clear.
Here, we investigated the potential crosstalk between FGFR4 and EGFR, and the effect of anti-EGFR therapy in the treatment of colon cancer. To explore the biological role of FGFR4 in cancer development, RNA-seq is done by using a colon cell line transfected FGFR4. Gene ontology data showed upregulation of genes related to EGFR signaling and we identified that the secret of FGFR4 excess EGFR ligands such as AREG with the activation of EGFR and erbB3 result. These results also demonstrated in vivo study and cooperative interaction of EGFR and FGFR4 promoted tumor growth. In addition, reduced excess FGFR4 cetuximab-induced cytotoxicity and FGFR4 inhibitor combinations (BLU9931) and cetuximab showed profound antitumor effect of cetuximab alone.
Clinically, we found a positive correlation between FGFR4 and AREG expression in tumor tissue but not in normal tissue of the colon cancer patients and these expressions were significantly correlated with poor overall survival in patients treated with cetuximab. Therefore, our results provide a novel mechanism of FGFR4 in connection with the activation of EGFR and FGFR4 inhibitors and cetuximab combination may be a promising therapeutic option to achieve an optimal response to anti-EGFR therapies in colon cancer.
fibroblast growth factor receptor (FGFRs) are often altered in a variety of human cancer cells and is expressed in hepatocellular carcinoma (HCC). Some literature has proven that cell lines HepG2 and Hep3B and we used PD173074, FGFR4 inhibitor, to explore the role of FGFR4 and the underlying mechanisms in the cell lines.
The results showed that a significant PD173074 HepG2 and Hep3B cells arrested in the G1 phase and inhibited cell proliferation. Furthermore, Western blot analysis revealed that PD173074 decreased levels of P-FRS2α, P-ERK, Cdk2, cyclin E and NF-kB (p65) in the core while increasing the level of ubiquitin and CUL3, an E3 ubiquitin ligase that involves the degradation of cyclin E.
FGFR4 increases EGFR signaling by inducing AREG expression and attenuates response to EGFR inhibitors in colon cancer
Thermosensitive poloxamer hydrogel heparin-packed bFGF and NGF to treat spinal cord injury
The application of growth factors (GFs) to treat chronic spinal cord injury (SCI) has been shown to promote axonal regeneration and functional recovery. However, the direct administration of the GFS is limited by the rapid degradation and dilution in the injured site. In addition, SCI recovery is a multifactorial process that requires multiple GFS to participate in tissue regeneration.
Based on these facts, controlled delivery of multiple growth factors (GFs) into the lesion area into an attractive strategy to improve SCI. Currently, we develop GFS-based delivery system (called GFS-HP) consisting of basic fibroblast growth factor (bFGF), nerve growth factor (NGF) and heparin-poloxamer (HP) hydrogels through self-assembly mode.
Description: A polyclonal antibody against FGF23. Recognizes FGF23 from Human. This antibody is Unconjugated. Tested in the following application: WB, ELISA;WB:1/500-1/2000.ELISA:1/20000
Description: A polyclonal antibody against Fgf23. Recognizes Fgf23 from Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB; Recommended dilution: WB:1:1000-1:5000
Description: A polyclonal antibody against FGF23. Recognizes FGF23 from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: WB, IF, ELISA;WB:1/500-1/2000.IF:1/200-1/1000.ELISA:1/20000
Description: A polyclonal antibody against FGF23. Recognizes FGF23 from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IF; Recommended dilution: IF:1:50-1:200
Description: A polyclonal antibody against FGF23. Recognizes FGF23 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IF;WB:1:500-1:3000, IF:1:100-1:500
Description: A polyclonal antibody against FGF23. Recognizes FGF23 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IF;WB:1:500-1:3000, IF:1:100-1:500
Description: Fibroblast growth factor 23 is a protein that in humans is encoded by the FGF23 gene. This gene encodes a member of the fibroblast growth factor family of proteins, which possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. The product of this gene regulates phosphate homeostasis and transport in the kidney. The full-length, functional protein may be deactivated via cleavage into N-terminal and C-terminal chains. Mutation of this cleavage site causes autosomal dominant hypophosphatemic rickets (ADHR). Mutations in this gene are also associated with hyperphosphatemic familial tumoral calcinosis (HFTC).
Description: FGF-23 is a protein of ∼30 kDa that is proteolytically processed to generate smaller N-terminal (18 kDa) and C-terminal (12 kDa) fragments. The N-terminal fragment of FGF-23 contains the FGF receptor (FGFR)-binding domain. In vivo studies using synthetic peptides have indicated that neither of the processed N-terminal or C-terminal fragments of FGF-23 can influence serum phosphate levels. FGF-23 can decrease the activity of NaPi-2a and NaPi-2c cotransporters to reduce renal phosphate reabsorption and thereby can increase urinary phosphate excretion. Similarly, FGF-23 can suppress the expression of 1-alpha-hydroxylase to reduce the production of the active vitamin D metabolite 1,25(OH)2D. Moreover, FGF-23 can also induce 24- hydroxylase, which degrades 1,25(OH)2D
Description: FGF-23 is a protein of ∼30 kDa that is proteolytically processed to generate smaller N-terminal (18 kDa) and C-terminal (12 kDa) fragments. The N-terminal fragment of FGF-23 contains the FGF receptor (FGFR)-binding domain. In vivo studies using synthetic peptides have indicated that neither of the processed N-terminal or C-terminal fragments of FGF-23 can influence serum phosphate levels. FGF-23 can decrease the activity of NaPi-2a and NaPi-2c cotransporters to reduce renal phosphate reabsorption and thereby can increase urinary phosphate excretion. Similarly, FGF-23 can suppress the expression of 1-alpha-hydroxylase to reduce the production of the active vitamin D metabolite 1,25(OH)2D. Moreover, FGF-23 can also induce 24- hydroxylase, which degrades 1,25(OH)2D
It GFS-HP is a kind of thermosensitive hydrogel that is suitable for administration in vivo orthotopic. Meanwhile, the 3D porous structure of the hydrogel is commonly used to load large quantities GFs.After GFS-HP single injection into the spinal cord lesion, sustained release of NGF and bFGF from HP can significantly improve the survival of neurons, axons regenerate, oppression astrogliosis reactive and recovery of locomotor, when compared with GFS treatment free or HP.
Felicia
