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Genome-Wide Screen for Context-Dependent Tumor Suppressors Identified Using in Vivo Models for Neoplasia in Drosophila.
G3: Genes, Genomes, Genetics ( IF 2.1 ) Pub Date : 2020-09-01 , DOI: 10.1534/g3.120.401545
Casper Groth 1, 2 , Pooja Vaid 1 , Aditi Khatpe 1 , Nelchi Prashali 1 , Avantika Ahiya 1 , Diana Andrejeva 2 , Madhumita Chakladar 1 , Sanket Nagarkar 1 , Rachel Paul 1 , Devaki Kelkar 1 , Teresa Eichenlaub 2 , Hector Herranz 2 , T S Sridhar 3 , Stephen M Cohen 2 , L S Shashidhara 4, 5
Affiliation  

Genetic approaches in Drosophila have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer in vivo. 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 in vivo. 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.



中文翻译:

全基因组屏幕的上下文相关的肿瘤抑制子使用果蝇中瘤形成的体内模型确定。

果蝇的遗传学方法已经成功地确定了许多与体内生长调控有关的基因以及与癌症的发生和发展有关的遗传相互作用。在这里,我们报告基于大型RNAi的筛选,以鉴定与已知的癌症驱动因子相互作用的潜在肿瘤抑制基因:表皮生长因子受体和河马途径转录辅因子Yorkie。设计这些筛选方法是为了鉴定其耗尽基因,使体内表达EGFR或Yki的组织从良性过度生长状态转化为体内赘生性转化。我们还报告了旨在确定其耗竭抑制在现有的EGFR依赖的瘤形成模型中肿瘤形成的基因的独立筛选。已知这里鉴定出的许多阳性在生长控制途径中起作用。我们还发现了许多与Yki和EGFR驱动的组织生长有关的新颖联系,其中多数是二者之一所独有的。因此,这里提供的资源对于研究在激活的EGFR和/或Yki的情况下在发育和癌症过程中生长的负调节剂以及在激活的EGFR的背景下研究生长的正调节剂的所有研究人员都是有用的。此处报告的资源可供任何人免费使用。

更新日期:2020-09-02
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