Defining the KRAS-and ERK-dependent transcriptome in KRAS-mutant cancers
Science, 2024•science.org
How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we
established a systemwide portrait of KRAS-and extracellular signal–regulated kinase (ERK)–
dependent gene transcription in KRAS-mutant cancer to delineate the molecular
mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene
signature diverges substantially from the frequently cited Hallmark KRAS signaling gene
signature, is driven predominantly through the ERK mitogen-activated protein kinase …
established a systemwide portrait of KRAS-and extracellular signal–regulated kinase (ERK)–
dependent gene transcription in KRAS-mutant cancer to delineate the molecular
mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene
signature diverges substantially from the frequently cited Hallmark KRAS signaling gene
signature, is driven predominantly through the ERK mitogen-activated protein kinase …
How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and extracellular signal–regulated kinase (ERK)–dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges substantially from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome (APC/C) and other components of the cell cycle machinery as key processes that drive pancreatic ductal adenocarcinoma (PDAC) growth. Our findings elucidate mechanistically the critical role of ERK in driving KRAS-mutant tumor growth and in resistance to KRAS-ERK MAPK targeted therapies.
![](/scholar/images/qa_favicons/sciencemag.org.png)
以上显示的是最相近的搜索结果。 查看全部搜索结果