Programmed cell fusion in development and homeostasis

Iosilevskii, Yael; Podbilewicz, Benjamin

doi:10.1016/bs.ctdb.2020.12.013

Cited by 13 publications

(11 citation statements)

References 146 publications

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“…Fusogens are indispensable for cellular hybridization to overcome fusion-associated energetic barriers [3][4][5][6][7][8]19,20] and thus, have to be expressed by fusion competent cells. Whereas cell fusion could occur in the presence or absence of inflammation [60,63,[76][77][78][79][80][81][82][83][84] it can be further concluded that the presence of distinct fusogens and associated relevant factors is either induced or constitutively expressed at basal expression levels.…”

Section: Viral-and Human Endogenous Retroviral-derived Fusogensmentioning

confidence: 99%

“…However, despite increasing knowledge the entire mechanism is still scarcely understood. The merging of two plasma membranes is a multi-step process of various proteins and fusogens that have been identified as indispensable mediators of cell-cell fusion to overcome plasma membrane merging-associated energetic barriers [3][4][5][6][7][8]19,20,89]. Enveloped and some non-enveloped viruses could induce syncytia/MNGC formation due to the expression of evolutionarily optimized fusogens [50,51,[121][122][123] whereby oncogenic viruses could lead to PGCC formation [21,206,219].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Cell fusion represents a fundamental biological mechanism, which is mandatory for physiological processes such as fertilization, placentation, myogenesis, osteoclastogenesis and wound healing/tissue repair [1][2][3][4][5][6][7]. Likewise, cell fusion plays an important role during pathophysiological conditions including tumor development.…”

Section: Introductionmentioning

confidence: 99%

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Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Dittmar

Weiler

Luo

et al. 2021

Cancers

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Cell fusion is a well-known, but still scarcely understood biological phenomenon, which might play a role in cancer initiation, progression and formation of metastases. Although the merging of two (cancer) cells appears simple, the entire process is highly complex, energy-dependent and tightly regulated. Among cell fusion-inducing and -regulating factors, so-called fusogens have been identified as a specific type of proteins that are indispensable for overcoming fusion-associated energetic barriers and final merging of plasma membranes. About 8% of the human genome is of retroviral origin and some well-known fusogens, such as syncytin-1, are expressed by human (cancer) cells. Likewise, enveloped viruses can enable and facilitate cell fusion due to evolutionarily optimized fusogens, and are also capable to induce bi- and multinucleation underlining their fusion capacity. Moreover, multinucleated giant cancer cells have been found in tumors derived from oncogenic viruses. Accordingly, a potential correlation between viruses and fusogens of human endogenous retroviral origin in cancer cell fusion will be summarized in this review.

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Section: Viral-and Human Endogenous Retroviral-derived Fusogensmentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Dittmar

Weiler

Luo

et al. 2021

Cancers

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“…The fusogen EFF-1 and its paralog AFF-1 fuse one-third of all the somatic cells in the skin, excretory, reproductive, nervous and digestive systems of nematodes. The functions of these cellular fusions are to sculpt cells, tissues, and organs to restrict cellular fates for a robust development 11 . In the absence of sequence similarity between EFF-1, AFF-1, and other known proteins, predictions of the structure of AFF-1 suggested structural similarity to class II viral fusogens 12 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of archaeal fusexins homologous to eukaryotic HAP2/GCS1 gamete fusion proteins

Moi

Nishio

et al. 2022

Nat Commun

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Sexual reproduction consists of genome reduction by meiosis and subsequent gamete fusion. The presence of genes homologous to eukaryotic meiotic genes in archaea and bacteria suggests that DNA repair mechanisms evolved towards meiotic recombination. However, fusogenic proteins resembling those found in gamete fusion in eukaryotes have so far not been found in prokaryotes. Here, we identify archaeal proteins that are homologs of fusexins, a superfamily of fusogens that mediate eukaryotic gamete and somatic cell fusion, as well as virus entry. The crystal structure of a trimeric archaeal fusexin (Fusexin1 or Fsx1) reveals an archetypical fusexin architecture with unique features such as a six-helix bundle and an additional globular domain. Ectopically expressed Fusexin1 can fuse mammalian cells, and this process involves the additional globular domain and a conserved fusion loop. Furthermore, archaeal fusexin genes are found within integrated mobile elements, suggesting potential roles in cell-cell fusion and gene exchange in archaea, as well as different scenarios for the evolutionary history of fusexins.

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“…Cell-cell fusion is a physiological process required for embryonic development and the formation of skeletal muscle, osteoclasts, and syncytiotrophoblasts 19 . In adult tissue, heterotypic cell-cell fusion is rare, though it can be detected during tissue repair and chronic in ammation 20 21 .…”

Section: Introductionmentioning

confidence: 99%

Cancer cell-macrophage fusion increases tumor cell heterogeneity and reshapes their microenvironment

Basile

Mallya

et al. 2022

Preprint

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The trademark of cancer is the ability to evolve, which lays the grounds for progressive events such as metastasis and recurrence. Although genetic mutations and epigenetic changes have been implicated as the mechanisms, they don’t explain why many cancers develop leukocytic traits. Cell fusion between cancer and somatic cells, particularly macrophages, has been suggested as an alternative pathway for cancer cells to obtain new traits via acquiring exogenous genetic material. In this study, tumor-macrophage hybrid cells were generated, and two clones, both grew slowly yet with very different tumorigenicity, were selected for further study. Despite their very different abilities to form tumors in mice, both clones showed significant abilities to influence the tumor microenvironment. RNA-seq of the hybrid cell clones revealed the differential expression profiles of the hybrid cells that contributed to the biological behaviors. This study emphasizes the role of hybrid cells as potent environmental modifiers that aid tumor survival and evolution despite their minority status among the tumor cells. This study also provides an animal experimental platform to study cancer-myeloid fusion and a potential direction for novel therapeutic interventions.

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Programmed cell fusion in development and homeostasis

Cited by 13 publications

References 146 publications

Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Discovery of archaeal fusexins homologous to eukaryotic HAP2/GCS1 gamete fusion proteins

Cancer cell-macrophage fusion increases tumor cell heterogeneity and reshapes their microenvironment

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