Mutation Detection of Fibroblast Growth Factor Receptor 3 for Infiltrative Hepatocellular Carcinoma by Whole-Exome Sequencing

Yan, Xiaopeng; Shao, Chao‐Peng; Chen, Chuang; Chen, Jun; Gu, Song; Huang, Luoshun; Xu, Feifei; Zhao, Hui; Qiu, Yudong

doi:10.1007/s10620-016-4408-7

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…non‐coding FGFR3‐antisense transcripts may increase FGFR3 mRNA stability and expression in tumour cells 26 . Higher FGFR3 protein levels occurred in 24% of HCC harbouring a FGFR3 gene with single nucleotide mutations in exon 9, 11 or 12 27 . Every third HCC expresses a FGFR3 splice variant lacking partly Ig‐like‐III domain but binding FGF1/2 at normal levels 28 .…”

Section: Discussionmentioning

confidence: 99%

Interaction of FGF9 with FGFR3‐IIIb/IIIc, a putative driver of growth and aggressive behaviour of hepatocellular carcinoma

Paur

Valler

Sienel

et al. 2020

Liver International

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Background & Aims Recently, overexpression of the fibroblast growth factor receptor 3 (FGFR3) splice variants FGFR3‐IIIb and FGFR3‐IIIc was found in ~50% of hepatocellular carcinoma (HCC). Here, we aim to identify FGFR3‐IIIb/IIIc ligands, which drive the progression of HCC. Methods FACS, MTT assay and/or growth curves served to identify the FGFR3‐IIIb/IIIc ligand being most effective to induce growth of hepatoma/hepatocarcinoma cell lines, established from human HCC. The most potent FGF was characterized regarding the expression levels in epithelial and stromal cells of liver and HCC and impact on neoangiogenesis, clonogenicity and invasive growth of hepatoma/hepatocarcinoma cells. Results Among all FGFR3‐IIIb/IIIc ligands tested, FGF9 was the most potent growth factor for hepatoma/hepatocarcinoma cells. Replication and/or sprouting of blood/lymphendothelial cells was stimulated as well. FGF9 occurred mainly in stromal cells of unaltered liver but in epithelial cells of HCC. Every fifth HCC exhibited overexpressed FGF9 and frequent co‐upregulation of FGFR3‐IIIb/IIIc. In hepatoma/hepatocarcinoma cells FGF9 enhanced the capability for clonogenicity and disintegration of the blood and lymphatic endothelium, being most pronounced in cells overexpressing FGFR3‐IIIb or FGFR3‐IIIc, respectively. Any of the FGF9 effects in hepatoma/hepatocarcinoma cells was blocked completely by applying the FGFR1‐3‐specific tyrosine kinase inhibitor BGJ398 or siFGFR3, while siFGFR1/2/4 were mostly ineffective. Conclusions FGF9 acts via FGFR3‐IIIb/IIIc to enhance growth and aggressiveness of HCC cells. Accordingly, blockade of the FGF9‐FGFR3‐IIIb/IIIc axis may be an efficient therapeutic option for HCC patients.

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Section: Discussionmentioning

confidence: 99%

Interaction of FGF9 with FGFR3‐IIIb/IIIc, a putative driver of growth and aggressive behaviour of hepatocellular carcinoma

Paur

Valler

Sienel

et al. 2020

Liver International

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“…259 MiR-99a-5p also directly binds to FGFR3 to inhibit mTOR signaling. 260 Mutations in FGFR3 are also present in hepatocellular carcinoma (HCC) 261 and renal cell carcinoma. 262 FGFR3 regulates angiogenesis and metastasis in HCC by increasing the level of monocyte chemotactic protein 1.…”

Section: Fgfr3 Functions As a Promoter In Tumorsmentioning

confidence: 99%

FGFR families: biological functions and therapeutic interventions in tumors

Liu,

Huang,

Yan

et al. 2023

MedComm

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There are five fibroblast growth factor receptors (FGFRs), namely, FGFR1–FGFR5. When FGFR binds to its ligand, namely, fibroblast growth factor (FGF), it dimerizes and autophosphorylates, thereby activating several key downstream pathways that play an important role in normal physiology, such as the Ras/Raf/mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase, phosphoinositide 3‐kinase (PI3K)/AKT, phospholipase C gamma/diacylglycerol/protein kinase c, and signal transducer and activator of transcription pathways. Furthermore, as an oncogene, FGFR genetic alterations were found in 7.1% of tumors, and these alterations include gene amplification, gene mutations, gene fusions or rearrangements. Therefore, FGFR amplification, mutations, rearrangements, or fusions are considered as potential biomarkers of FGFR therapeutic response for tyrosine kinase inhibitors (TKIs). However, it is worth noting that with increased use, resistance to TKIs inevitably develops, such as the well‐known gatekeeper mutations. Thus, overcoming the development of drug resistance becomes a serious problem. This review mainly outlines the FGFR family functions, related pathways, and therapeutic agents in tumors with the aim of obtaining better outcomes for cancer patients with FGFR changes. The information provided in this review may provide additional therapeutic ideas for tumor patients with FGFR abnormalities.

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“…The supernatants were concentrated by ultracentrifugation at 25,000 x rpm at 4˚C for 2 h, and the lentiviral particle pellet was resuspended in 100% FBS and stored at -80˚C. The viral titers of concentrated lentiviral particles were measured by infecting 293T cells seeded at a density of 4x10 4 cells/well in a 96-well plate with viral serial dilutions. Green fluorescent protein (GFP) expression was detected 4 days later under a fluorescence microscope and the viral titer was calculated using the following equation: Viral titer (Tu/µl)=(% GFP + cells x number of cells transduced)/virus volume.…”

Section: Methodsmentioning

confidence: 99%

“…In recent years, the incidence of liver cancer has been on the rise, yet <20% of patients receive timely radical surgical resection, due to the high degree of malignancy, early metastasis and high invasion potential of this tumor type. These properties are often associated with the complex biochemical regulatory behavior of HCC cells, such as excessive cell proliferation (3,4). Although HCC treatment methods and efficiency have improved the 5-year survival rate, several methods such as radical resection, transcatheter arterial chemoembolization, sorafenib and chemoradiotherapy still have their respective limits (5).…”

Section: Introductionmentioning

confidence: 99%

CSN1 facilitates proliferation and migration of hepatocellular carcinoma cells by upregulating cyclin A2 expression

Zhang

Yin

et al. 2020

Mol Med Rep

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Constitutive photomorphogenesis 9 signalosome subunit 1 (CSN1) plays an important role in the ubiquitin-proteasome pathway and regulates various cellular processes, such as the cell cycle and DNA repair. The CSN complex consists of eight subunits (CSN1 to CSN8) and regulates the tumorigenesis of a variety of tumor types. However, the exact role of CSN1 in hepatocellular carcinoma (HCC) remains unclear. The present study evaluated the expression and biological effects of CSN1 in HCC tissue samples and cell lines. CSN1 was significantly overexpressed in HCC tissue and cell lines, compared with their normal counterparts. In patients with HCC, elevated CSN1 levels correlated with tumor size, tumor metastasis and tumor stage. Loss-of-function assays indicated that CSN1 knockdown inhibited the proliferation and migration HCC cells. In addition, CSN1 promoted the expression of cyclin A2 in a ubiquitination-independent manner. Lastly, xenograft experiments indicated that CSN1 promoted HCC tumor growth in vivo . The present study suggested that CSN1 inhibition could represent a potential approach for the prevention of HCC progression and metastasis.

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Mutation Detection of Fibroblast Growth Factor Receptor 3 for Infiltrative Hepatocellular Carcinoma by Whole-Exome Sequencing

Abstract: Our studies indicated that FGFR3 may be a candidate oncogene in tumor progression and a promising therapeutic target in iHCC patients who had early recurrence.

Cited by 5 publications

References 39 publications

Interaction of FGF9 with FGFR3‐IIIb/IIIc, a putative driver of growth and aggressive behaviour of hepatocellular carcinoma

Interaction of FGF9 with FGFR3‐IIIb/IIIc, a putative driver of growth and aggressive behaviour of hepatocellular carcinoma

FGFR families: biological functions and therapeutic interventions in tumors

CSN1 facilitates proliferation and migration of hepatocellular carcinoma cells by upregulating cyclin A2 expression

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