Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS–MAPK Pathway Inhibition in Pancreatic Cancer

Abstract excerpt

The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS-MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the...

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