Atypical KRAS^G12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer.

ABSTRACT: Allele-specific signaling by different KRAS alleles remains poorly understood. The KRAS ^G12R mutation displays uneven prevalence among cancers that harbor the highest occurrence of KRAS mutations: It is rare (∼1%) in lung and colorectal cancers, yet relatively common (∼20%) in pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether KRAS^G12R is functionally distinct from the more common KRAS^G12D- or KRAS^G12V-mutant proteins (KRAS^G12D/V). We found that KRAS^G12D/V but not KRAS^G12R drives macropinocytosis and that MYC is essential for macropinocytosis in KRAS^G12D/V- but not KRAS^G12R-mutant PDAC. Surprisingly, we found that KRAS^G12R<

SUBMITTER: Hobbs GA 

PROVIDER: S-EPMC6954322 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature