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The Dark Side of Cell Fusion - PubMed

  • ️Fri Jan 01 2016

Review

The Dark Side of Cell Fusion

Daniel Bastida-Ruiz et al. Int J Mol Sci. 2016.

Abstract

Cell fusion is a physiological cellular process essential for fertilization, viral entry, muscle differentiation and placental development, among others. In this review, we will highlight the different cancer cell-cell fusions and the advantages obtained by these fusions. We will specially focus on the acquisition of metastatic features by cancer cells after fusion with bone marrow-derived cells. The mechanism by which cancer cells fuse with other cells has been poorly studied thus far, but the presence in several cancer cells of syncytin, a trophoblastic fusogen, leads us to a cancer cell fusion mechanism similar to the one used by the trophoblasts. The mechanism by which cancer cells perform the cell fusion could be an interesting target for cancer therapy.

Keywords: cancer; cell fusion; drug resistance; metastasis; syncytin.

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Figures

Figure 1
Figure 1

Multinucleated human ovarian cancer cell isolated from malignant ascites. The cells are labeled with DAPI (nucleus, blue) and Phalloidin (actin, red) and observed by confocal microscopy at magnification 400×. Scale bars: 20 µm. The white arrow indicates the multinucleated cell.

Figure 2
Figure 2

Cell fusion mediated by syncytin 1. (A) Schematic portrait of syncytin 1 structure. The signal peptide domain is represented in light blue. The surface unit (SU) is represented in yellow and contains a receptor binding domain (RBD; SDGGGX2DX2R) and a CXXC motif. The transmembrane unit (TM) contains a fusion peptide represented in red, heptad repeats 1 (HR1) represented in purple, heptad repeats 2 (HR2) represented in pink, a transmembrane domain represented in black, an intracytoplasmic domain represented in green and a CX6CC domain. Between the SU and the TM is a furin cleavage site (RNKR) represented in light red. The Y indicate N-glycosylation sites and numbers indicate the amino acid position. A disulfide bond is formed between the CXXC motif of SU and the CX6CC domain of TM; (B) Schematic representation of syncytin 1-dependent cell fusion. (a) Resting stage; (b) RBD (yellow) binding to the hASCT2 receptor (light green); (c) Disulfide bond breaking and removing of SU domains, producing a conformational change in syncytin 1 protein leading to the insertion of the fusion peptide (red) into the cell membrane; (d) Assembly of HR2 (pink) and HR1 (purple); (e) Final stage with the membranes in close proximity and initiation of membrane bending. Adapted from [106,107].

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