Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune 411008, India.
Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200N, Denmark.
G3 (Bethesda). 2020 Sep 2;10(9):2999-3008. doi: 10.1534/g3.120.401545.
Genetic approaches in have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer Here, we report on large-scale RNAi-based screens to identify potential tumor suppressor genes that interact with known cancer-drivers: the Epidermal Growth Factor Receptor and the Hippo pathway transcriptional cofactor Yorkie. These screens were designed to identify genes whose depletion drove tissue expressing EGFR or Yki from a state of benign overgrowth into neoplastic transformation We also report on an independent screen aimed to identify genes whose depletion suppressed formation of neoplastic tumors in an existing EGFR-dependent neoplasia model. Many of the positives identified here are known to be functional in growth control pathways. We also find a number of novel connections to Yki and EGFR driven tissue growth, mostly unique to one of the two. Thus, resources provided here would be useful to all researchers who study negative regulators of growth during development and cancer in the context of activated EGFR and/or Yki and positive regulators of growth in the context of activated EGFR. Resources reported here are available freely for anyone to use.
在 方面的遗传方法已成功鉴定出许多参与生长调控的基因，以及与癌症起始和进展相关的遗传相互作用。在这里，我们报告了大规模的基于 RNAi 的筛选，以鉴定与已知的癌症驱动因子：表皮生长因子受体和 Hippo 通路转录共激活因子 Yorkie 相互作用的潜在肿瘤抑制基因。这些筛选旨在鉴定那些耗尽后会导致表达 EGFR 或 Yki 的组织从良性过度生长状态转变为肿瘤转化的基因。我们还报告了一项旨在鉴定在现有的 EGFR 依赖性肿瘤模型中抑制肿瘤形成的基因的独立筛选。这里鉴定的许多阳性基因已知在生长控制途径中具有功能。我们还发现了许多与 Yki 和 EGFR 驱动的组织生长有关的新联系，其中大多数与两者中的一个有关。因此，对于所有研究在激活的 EGFR 和/或 Yki 背景下发育和癌症中生长的负调控因子以及在激活的 EGFR 背景下生长的正调控因子的人来说，这里提供的资源将非常有用。这里报告的资源可供任何人免费使用。
