Translational Hematology and Oncology (THOR), Cleveland Clinic, Cleveland, OH 44120, USA; School of Medicine, Case Western Reserve University, Cleveland, OH 44120, USA.
Translational Hematology and Oncology (THOR), Cleveland Clinic, Cleveland, OH 44120, USA; Oslo University Hospital, Ullevål, Department of Medical Genetics, Oslo, Norway.
Int J Biochem Cell Biol. 2024 Oct;175:106649. doi: 10.1016/j.biocel.2024.106649. Epub 2024 Aug 24.
In this review, we consider the role of cell-cell fusion in cancer development and progression through an evolutionary lens. We begin by summarizing the origins of fusion proteins (fusogens), of which there are many distinct classes that have evolved through convergent evolution. We then use an evolutionary framework to highlight how the persistence of fusion over generations and across different organisms can be attributed to traits that increase fitness secondary to fusion; these traits map well to the expanded hallmarks of cancer. By studying the tumor microenvironment, we can begin to identify the key selective pressures that may favor higher rates of fusion compared to healthy tissues. The paper concludes by discussing the increasing number of research questions surrounding fusion, recommendations for how to answer them, and the need for a greater interest in exploring cell fusion and evolutionary principles in oncology moving forward.
在这篇综述中，我们从进化的角度探讨了细胞融合在癌症发展和演进中的作用。我们首先总结了融合蛋白（fusogens）的起源，其中有许多不同的类别是通过趋同进化而演化出来的。然后，我们利用进化框架来强调融合在几代人和不同生物体中的持续存在，可以归因于那些由于融合而增加适应性的特征；这些特征与癌症的扩展特征很好地契合。通过研究肿瘤微环境，我们可以开始确定可能有利于融合发生的关键选择压力，与健康组织相比，融合发生的频率更高。本文最后讨论了围绕融合的越来越多的研究问题，以及回答这些问题的建议，同时还强调了人们需要进一步关注探索肿瘤学中的细胞融合和进化原则。
