Harun Ozturk, Harun Cingoz, Turan Tufan, Jiekun Yang, Sara J Adair, Krishna Seshu Tummala, Cem Kuscu, Meric Kinali, Gamze Comertpay, Sarbajeet Nagdas, Bernadette J Goudreau, Husnu Umit Luleyap, Yagmur Bingul, Timothy B Ware, Wiliam L Hwang, Ku-Lung Hsu, David F Kashatus, David T Ting, Navdeep S Chandel, Nabeel Bardeesy, Todd W Bauer, Mazhar Adli
Pancreatic ductal adenocarcinoma (PDA) cells reprogram their transcriptional and metabolic programs to survive the nutrient-poor tumor microenvironment. Through in vivo CRISPR screening, we discovered islet-2 (ISL2) as a candidate tumor suppressor that modulates aggressive PDA growth. Notably, ISL2, a nuclear and chromatin-associated transcription factor, is epigenetically silenced in PDA tumors and high promoter DNA methylation or its reduced expression correlates with poor patient survival. The exogenous ISL2 expression or CRISPR-mediated upregulation of the endogenous loci reduces cell proliferation...
June 6, 2022: Developmental Cell