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

Simple Summary: Even though it is known that (cancer) cells can fuse, it is still less understood how (cancer) cells merge their plasma membranes, thereby giving rise to bi- and multinucleated hybrid cells. Cell-cell fusion is an energy-dependent process and so-called fusogens are a crucial type of membrane-bound proteins, which are mandatory for overcoming plasma membrane hybridization with associated energetic barriers. Viruses and fusogens of human endogenous retroviral elements are a natural reservoir of fusogenic particles and proteins that could cause bi- and multinucleation of cancer cells. Likewise, multinucleated giant cancer cells have been found in several cancers caused by oncogenic viruses suggesting a possible correlation between viruses and fusogens of human endogenous retroviral origin in cancer cell fusion. 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.

Automated summary

Cell fusion in cancer cells involving fusion proteins is a complex and energy-dependent process, potentially related to viruses and human endogenous retroviral elements. The phenomenon of multinucleation and fusion capacity may play a role in cancer initiation, progression, and metastasis, with syncytin-1 and enveloped viruses contributing to the fusion process. This review summarizes the potential correlation between viruses and fusogens of human endogenous retroviral origin in cancer cell fusion.