ELUCIDATING MECHANISMS OF CELL COMPETITION DURING DEVELOPMENT -Equipment supplement

项目摘要 这项提案的目标是了解细胞竞争如何调节组织生长 以及在癌症等疾病期间，这种机制如何被颠覆。我们的实验室和其他实验室 已经表明，相邻种群之间的遗传异质性会引发竞争性相互作用 在他们之间，导致有选择地淘汰较弱的人口(失败者)和扩大 强者(赢家)。在经典的细胞竞争中，野生型细胞淘汰了有活力但不是最优的细胞 细胞。这种类型的细胞竞争起到了质量控制机制的作用，以选择性地去除次优 组织中的细胞。在超级竞争中，具有更高水平的癌基因的细胞，如STAT和Myc，会杀死他们的 野性的邻居。超竞争在癌症进展和转移过程中发挥作用。虽然很有竞争力 相互作用是保守的，并且越来越多地被很好地记录下来，调节消除 人们对较弱的细胞或较强的细胞的扩张知之甚少。通过下一代 测序后，我们确定了两个由STAT获胜者产生的可溶性应激反应因子 促进他们的竞技体能。在这里，我们将测试这些因素在细胞竞争中的作用。目标1专注于 论损伤-反应通路在超级杯比赛中对失败者不利或提高获胜者体能的作用 竞争。目标2将测试细胞外的活性氧物种在杀死失败者和/或促进 赢家在经典细胞竞争和超竞争中都起着作用。我们设想，我们的研究将 阐明癌前细胞在组织内建立自身所使用的分子和细胞事件 当这些细胞发展成完全肿瘤性病变时，这可能是可行的。

Project Summary The goal of this proposal is to understand how cell competition regulates tissue growth during development and how such mechanisms can be subverted during diseases like cancer. Our lab and other labs have shown that genetic heterogeneity between neighboring populations provokes competitive interactions between them, resulting in the selective elimination of the weaker population (the losers) and the expansion of the stronger one (the winners). During classical cell competition wild-type cells eliminate viable but sub-optimal cells. This type of cell competition functions as a quality control mechanism to selectively remove suboptimal cells from a tissue. During super-competition, cells with higher levels of oncogenes like STAT and Myc kill their wild-type neighbors. Super-competition functions during cancer progression and metastasis. While competitive interactions are conserved and are increasingly well documented, the mechanisms regulating the elimination of the weaker cells or the expansion of the stronger cells are poorly understood. Through next-generation sequencing, we identified two soluble stress-responsive factors that are produced by STAT winners and that promote their competitive fitness. Here, we will test the roles of these factors in cell competition. Aim 1 is focused on the role of the damage-response pathway in disadvantaging losers or increasing winner fitness in super- competition. Aim 2 will test the role of extracellular reactive oxygen species in killing losers and/or boosting winner function in both classical cell competition and super-competition. We envision that our studies will elucidate molecular and cellular events employed by pre-cancerous cells to establish themselves within a tissue and that might be operative when these cells progress into fully neoplastic lesions.