Rapid Fusion and Syncytium Formation of Heterologous Cells upon Expression of the FGFRL1 Receptor

Steinberg, Florian; Gerber, Simon; Rieckmann, Thorsten; Trüeb, Beat

doi:10.1074/jbc.m110.140517

Cited by 26 publications

(29 citation statements)

References 40 publications

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“…It was therefore concluded that FGFRL1 exerted a negative effect on cell proliferation. These experiments were later repeated with an inducible system utilizing HEK293-TetOn cells that express FGFRL1 from a construct, which is under the control of the Tet transactivator [38]. In the absence of the inducer doxycycline, these cells proliferated like normal HEK293 cells.…”

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

“…Recently, it has also been observed that FGFRL1 has a peculiar effect on cell-cell fusion [38]. The fusion of mammalian cells into large syncytia is a well controlled process that is restricted to a limited set of cells, including gametes, macrophages, myoblasts, and trophoblasts [39,40].…”

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

“…The fusion of mammalian cells into large syncytia is a well controlled process that is restricted to a limited set of cells, including gametes, macrophages, myoblasts, and trophoblasts [39,40]. Steinberg et al [38] demonstrated that the FGFRL1 receptor, when overexpressed, was capable of fusing CHO cells into multinucleated syncytia comprising several hundred nuclei. A particularly strong effect was observed with FGFRL1DC (a construct that lacked the intracellular domain but still retained the transmembrane domain), but cell fusion could also be induced with the full-length protein.…”

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

“…Truncation experiments further demonstrated that Ig domain D3 and the transmembrane domain were both necessary and sufficient for the fusion activity. The novel receptor was even able to fuse heterologous cells, such as HEK293 or HeLa cells, with untransfected CHO cells [38]. FGFRL1 is therefore the first mammalian protein that is capable of inducing syncytium formation of heterologous cells in vitro.…”

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

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Biology of FGFRL1, the fifth fibroblast growth factor receptor

Trüeb

2010

Cell. Mol. Life Sci.

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124

102

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FGFRL1 (fibroblast growth factor receptor like 1) is the most recently discovered member of the FGFR family. It contains three extracellular Ig-like domains similar to the classical FGFRs, but it lacks the protein tyrosine kinase domain and instead contains a short intracellular tail with a peculiar histidine-rich motif. The gene for FGFRL1 is found in all metazoans from sea anemone to mammals. FGFRL1 binds to FGF ligands and heparin with high affinity. It exerts a negative effect on cell proliferation, but a positive effect on cell differentiation. Mice with a targeted deletion of the Fgfrl1 gene die perinatally due to alterations in their diaphragm. These mice also show bilateral kidney agenesis, suggesting an essential role for Fgfrl1 in kidney development. A human patient with a frameshift mutation exhibits craniosynostosis, arguing for an additional role of FGFRL1 during bone formation. FGFRL1 contributes to the complexity of the FGF signaling system.

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Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

Section: Biological Effects Of Fgfrl1mentioning

confidence: 99%

See 2 more Smart Citations

Biology of FGFRL1, the fifth fibroblast growth factor receptor

Trüeb

2010

Cell. Mol. Life Sci.

Self Cite

124

102

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“…The rarity of fusion, the scarcity of reports and the difficulty of detection could explain why cell fusion remained poorly understood [9]. The fusion of mammalian cells into syncytia is regarded as a developmental process that is tightly restricted to a limited subset of cells [10]. HeLa cells expressing fusion proteins have been used to analyse glycoproteins in virus-induced cell fusion, leading to the conclusion that the expression of the fusion protein F enhances susceptibility to cell fusion [11].…”

Section: Introductionmentioning

confidence: 99%

Tumor Cell Fusion and Multipolar Trivision

Király¹

2013

Journal of Cancer Research and Therapeutic Oncology

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The fusogenic character of tumor cells has been suspected, without direct visualization of such processes. Fusion is likely to create polyploid cells, instability, chromosome loss, and induce tumorigenicity. The aim of this study was to provide direct evidence for the fusion and trivision of hyperploid tumor cells and their viability. Cell fusion was captured by time-lapse microscopy in hypertriploid (> 3N) HeLa cell culture followed by trivisions and seen with relatively high frequency (1:24, 4%) relative to cell divisions. The diameters of round M phase HeLa, HaCaT and uveal melanoma cells and their cell volumes before trivision were significantly larger than the size of cells to be divided, while the average volumes of trivided cells were smaller than divided cells. The volume of trivided smaller cells was not uniform indicating an uneven distribution of cytoplasmic material. We provide cinemicrophotographic evidence that after fusion the hybrid HeLa cell undergoes trivision and generates one large and two smaller cells. In the next cell cycle the larger daughter cell divides in two cells, the two smaller daughter cells fuse and trivide. Fused hybrid tumor cells are viable and generate further trivisions and divisions conforming to the cell fusion hypothesis suggesting that fusion generates aneuploid small tumor cells that can lead to metastasis.

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An integrated genomic, transcriptional and protein investigation of FGFRL1 as a putative 4p16.3 deletion target in bladder cancer

Martino

Taylor

Roulson

et al. 2013

Genes Chromosomes & Cancer

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Loss of heterozygosity (LOH) of chromosome arm 4p is a common event in bladder and other malignancies. At least three distinct regions of deletion have been identified, but the deletion targets have so far remained elusive. In this study, we have identified a novel region of deletion mapping to 4p16.3 spanning 0–2.1 Mb, in 15% of bladder tumors and 24% of bladder cancer cell lines. FGFRL1, which maps within this region, was investigated as putative deletion target. The retained FGFRL1 allele was not mutated in cell lines and tumors with LOH, although in patients heterozygous for the rs4647930 functional polymorphism, the common allele was preferentially lost in tumor tissue. Epigenetic silencing of the retained allele was also excluded as levels of FGFRL1 mRNA and protein were similar in cell lines and tumors with and without 4p16.3 loss. However, while FGFRL1 protein was moderately expressed in all layers of the normal bladder epithelium, the majority of tumors showed areas of downregulation. Overall, average FGFRL1 protein expression was significantly lower in bladder tumors compared to normal tissue, but downregulation was independent from 4p16.3 LOH status, FGFR3 mutation, and tumor grade and stage. In conclusion, although we found no evidence supporting a “two‐hit” inactivation of FGFRL1 in bladder carcinogenesis, the effect of heterozygous deletion coupled with functional polymorphisms, and the role of post‐transcriptional downregulation deserves further investigation. © 2013 Wiley Periodicals, Inc.

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Rapid Fusion and Syncytium Formation of Heterologous Cells upon Expression of the FGFRL1 Receptor

Cited by 26 publications

References 40 publications

Biology of FGFRL1, the fifth fibroblast growth factor receptor

Biology of FGFRL1, the fifth fibroblast growth factor receptor

Tumor Cell Fusion and Multipolar Trivision

An integrated genomic, transcriptional and protein investigation of FGFRL1 as a putative 4p16.3 deletion target in bladder cancer

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