Sanchez Bosch Pablo, Cho Bomsoo, Axelrod Jeffrey D
Department of Pathology, Stanford University School of Medicine, Stanford, United States.
Elife. 2024 Dec 30;13:RP98535. doi: 10.7554/eLife.98535.
The growth and survival of cells with different fitness, such as those with a proliferative advantage or a deleterious mutation, is controlled through cell competition. During development, cell competition enables healthy cells to eliminate less fit cells that could jeopardize tissue integrity, and facilitates the elimination of pre-malignant cells by healthy cells as a surveillance mechanism to prevent oncogenesis. Malignant cells also benefit from cell competition to promote their expansion. Despite its ubiquitous presence, the mechanisms governing cell competition, particularly those common to developmental competition and tumorigenesis, are poorly understood. Here, we show that in , the planar cell polarity (PCP) protein Flamingo (Fmi) is required by winners to maintain their status during cell competition in malignant tumors to overtake healthy tissue, in early pre-malignant cells when they overproliferate among wildtype cells, in healthy cells when they later eliminate pre-malignant cells, and by supercompetitors as they compete to occupy excessive territory within wildtype tissues. 'Would-be' winners that lack Fmi are unable to overproliferate, and instead become losers. We demonstrate that the role of Fmi in cell competition is independent of PCP, and that it uses a distinct mechanism that may more closely resemble one used in other less well-defined functions of Fmi.
具有不同适应性的细胞（例如具有增殖优势或有害突变的细胞）的生长和存活是通过细胞竞争来控制的。在发育过程中，细胞竞争使健康细胞能够消除可能危及组织完整性的适应性较差的细胞，并作为一种预防肿瘤发生的监测机制，促进健康细胞消除癌前细胞。恶性细胞也从细胞竞争中受益以促进其扩张。尽管细胞竞争普遍存在，但控制细胞竞争的机制，特别是那些发育竞争和肿瘤发生共有的机制，仍知之甚少。在这里，我们表明，在恶性肿瘤中，当赢家在细胞竞争中取代健康组织时、在癌前早期细胞在野生型细胞中过度增殖时、在健康细胞后来消除癌前细胞时以及超级竞争者在野生型组织中争夺过多领地时，平面细胞极性（PCP）蛋白弗拉明戈（Fmi）是赢家维持其地位所必需的。缺乏Fmi的“潜在”赢家无法过度增殖，反而成为输家。我们证明Fmi在细胞竞争中的作用独立于PCP，并且它使用一种独特的机制，该机制可能更类似于Fmi在其他定义不太明确的功能中所使用的机制。
