Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Graduate Program in Cell and Molecular Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Int J Mol Sci. 2021 Jan 7;22(2):518. doi: 10.3390/ijms22020518.
Cell competition (CC) is a feature that allows tumor cells to outcompete and eliminate adjacent cells that are deemed less fit. Studies of CC, first described in , reveal a diversity of underlying mechanisms. In this review, we will discuss three recent studies that expand our understanding of the molecular features governing CC. In particular, we will focus on a molecular fitness fingerprint, oncogenic pathways, and the importance of cell junction stability. A fitness fingerprint, mediated by flower (hFWE) protein isoforms, dictates that cells expressing the flower-win isoforms will outcompete adjacent flower-loss-expressing cells. The impact of the flower protein isoforms is seen in cancer progression and may have diagnostic potential. The yes-associated protein (YAP) and TAZ transcription factors, central mediators of the oncogenic Hippo pathway, elevate peritumoral fitness thereby protecting against tumor progression and provide a suppressive barrier. Similarly, COL17A1 is a key component in hemidesmosome stability, and its expression in epidermal stem cells contributes to fitness competition and aging characteristics. The contributions of these pathways to disease development and progression will help define how CC is hijacked to favor cancer growth. Understanding these features will also help frame the diagnostic and therapeutic possibilities that may place CC in the crosshairs of cancer therapeutics.
细胞竞争（CC）是一种使肿瘤细胞能够与被认为适应性较差的相邻细胞竞争并消除它们的特征。首先在 中描述的 CC 研究揭示了多种潜在的机制。在这篇综述中，我们将讨论最近的三项研究，这些研究扩展了我们对控制 CC 的分子特征的理解。特别是，我们将重点介绍分子适应性指纹、致癌途径以及细胞连接稳定性的重要性。由花（hFWE）蛋白异构体介导的适应性指纹决定了表达花赢型异构体的细胞将胜过相邻的花失活型表达细胞。花蛋白异构体的影响在癌症进展中可见，并且可能具有诊断潜力。yes 相关蛋白（YAP）和 TAZ 转录因子是致癌 Hippo 途径的核心介质，它们提高了肿瘤周围的适应性，从而防止肿瘤进展并提供抑制性障碍。同样，COL17A1 是半桥粒稳定性的关键组成部分，其在表皮干细胞中的表达有助于适应性竞争和衰老特征。这些途径对疾病发展和进展的贡献将有助于确定 CC 是如何被劫持以促进癌症生长的。了解这些特征也将有助于确定 CC 在癌症治疗中的诊断和治疗可能性。
