A whole-genome RNAi screen identifies an 8q22 gene cluster that inhibits death receptor-mediated apoptosis

摘要: Deregulation of apoptosis is a common occurrence in cancer, for which emerging oncology therapeutic agents designed to engage this pathway are undergoing clinical trials. With the aim uncovering strategies activate cancer cells, we used pooled shRNA screen interrogate death receptor signaling. This screening approach identified 16 genes that modulate sensitivity ligand induced apoptosis, with several exhibiting frequent overexpression and/or copy number gain cancer. Interestingly, two top hits, EDD1 and GRHL2, found 50 kb apart on chromosome 8q22, region frequently amplified many cancers. By using series silencing studies, show GRHL2 suppress death-receptor expression, expression elevated breast, pancreas, lung cell lines resistant receptor-mediated apoptosis. Supporting relevance as candidates either gene sensitizes 8q22-amplified breast Our findings highlight mechanism by cells may evade therefore provide insight search new targets functional biomarkers pathway.