Defective transcription elongation in human cancers imposes targetable proteotoxic vulnerability.

ABSTRACT: Successful cancer therapy is contingent on identifying cancer-specific aberrant phenotypes and their associated vulnerabilities. We recently reported that a subset of almost every cancer type contains a genome-wide defect in RNA Polymerase II-mediated transcription elongation (TE^def), which impairs the expression of long genes and confers resistance to anti-tumor immune attack. Using a combination of computational analysis and laboratory experiments, we report that tumor cells with TE^def have widespread overexpression of the components of the protein homeostasis machinery (mostly composed of short genes), including protein folding and clearance. Accordingly, TE^def cells were characterized by abnormally high levels of insoluble protein aggregates in the cyto

SUBMITTER: Muhammad B 

PROVIDER: S-EPMC8718660 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature