Department of Biochemistry, West Virginia University School of Medicine, Morgantown, WV, USA.
Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
EMBO J. 2021 Sep 1;40(17):e107271. doi: 10.15252/embj.2020107271. Epub 2021 Aug 9.
Tumors are complex cellular and acellular environments within which cancer clones are under continuous selection pressures. Cancer cells are in a permanent mode of interaction and competition with each other as well as with the immediate microenvironment. In the course of these competitive interactions, cells share information regarding their general state of fitness, with less-fit cells being typically eliminated via apoptosis at the hands of those cells with greater cellular fitness. Competitive interactions involving exchange of cell fitness information have implications for tumor growth, metastasis, and therapy outcomes. Recent research has highlighted sophisticated pathways such as Flower, Hippo, Myc, and p53 signaling, which are employed by cancer cells and the surrounding microenvironment cells to achieve their evolutionary goals by means of cell competition mechanisms. In this review, we discuss these recent findings and explain their importance and role in evolution, growth, and treatment of cancer. We further consider potential physiological conditions, such as hypoxia and chemotherapy, that can function as selective pressures under which cell competition mechanisms may evolve differently or synergistically to confer oncogenic advantages to cancer.
肿瘤是复杂的细胞和无细胞环境,其中癌症克隆受到持续的选择压力。癌细胞之间以及与周围微环境之间处于持续的相互作用和竞争状态。在这些竞争相互作用的过程中,细胞会共享有关其一般适应性状态的信息,适应性较差的细胞通常会通过细胞凋亡被那些具有更高细胞适应性的细胞所消灭。涉及细胞适应性信息交换的竞争相互作用会影响肿瘤的生长、转移和治疗结果。最近的研究强调了复杂的途径,如 Flower、Hippo、Myc 和 p53 信号通路,这些途径被癌细胞和周围微环境细胞用来通过细胞竞争机制实现其进化目标。在这篇综述中,我们讨论了这些最新的发现,并解释了它们在癌症的进化、生长和治疗中的重要性和作用。我们还进一步考虑了潜在的生理条件,如缺氧和化疗,这些条件可以作为选择压力,在这些条件下,细胞竞争机制可能会以不同的方式或协同进化,从而为癌症提供致癌优势。