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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA-seq to investigate impact of treatment of KRAS mutant NCI-H2009 lung adenocarcinoma cells with the multi-ERBB inhibitor Neratinib

ABSTRACT: KRAS mutation is widely presumed to confer independence from upstream RTK signalling, however emerging evidence from mouse models of lung cancer suggests that ERBB RTKs may amplify signalling through RAS isoforms and participate in mutant RAS-driven lung cancer. This is one of 3 datasets where we examined the transcriptional impact of treatment of KRAS mutant human lung cancer cell lines with the multi-ERBB inhibitor Neratinib

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Murphy

PROVIDER: E-MTAB-6486 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The ERBB network facilitates KRAS-driven lung tumorigenesis.

Kruspig Björn B Monteverde Tiziana T Neidler Sarah S Hock Andreas A Kerr Emma E Nixon Colin C Clark William W Hedley Ann A Laing Sarah S Coffelt Seth B SB Le Quesne John J Dick Craig C Vousden Karen H KH Martins Carla P CP Murphy Daniel J DJ

Science translational medicine 20180601 446

KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are ...[more]

PMID: 29925636

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RNA-seq to investigate impact of treatment of KRAS mutant A549 lung adenocarcinoma cells with the multi-ERBB inhibitor Neratinib

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2018-06-01 | E-MTAB-6483 | biostudies-arrayexpress

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Dual inhibition of KRASG12D and pan-ERBB is synergistic in pancreatic ductal adenocarcinoma

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Comparison of KrasG12D/WT;p53Fx/Fx and KrasG12D/G12D;p53Fx/Fx MEFs

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KRAS and YAP1 converge to regulate EMT and tumor survival

Project description:Cancer cells that express oncogenic alleles of RAS typically require sustained expression of the mutant allele for survival, but the molecular basis of this oncogene dependency remains incompletely understood. To identify genes that can functionally substitute for oncogenic RAS, we systematically expressed 15,294 open reading frames in a human KRAS-dependent colon cancer cell line engineered to express an inducible KRAS-specific shRNA. We found 147 genes that promoted survival in the setting of KRAS suppression. In this model, the transcriptional co-activator YAP1 rescued cell viability in KRAS-dependent cells upon suppression of KRAS and was required for KRAS-induced cell transformation. Acquired resistance to Kras suppression in a Kras-driven murine lung cancer model also involved increased YAP1 signaling. KRAS and YAP1 converge on the transcription factor FOS and activate a transcriptional program involved in regulating the epithelial-mesenchymal transition (EMT). Together, these findings implicate transcriptional regulation of EMT by YAP1 as a significant component of oncogenic RAS signaling Three biological replicates of primary lung adenocarcinoma cells derived from the Kras Lox-STOP-Lox-G12D;p53flox/flox (KP) mouse lung cancer model into which a doxycycline-inducible shRNA targeting Kras expressed from the 3’UTR of GFP was introduced (KP-KrasA cells) were analyzed at timepoints (days) D0, D4, and D21.

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2016-02-24 | E-GEOD-75871 | biostudies-arrayexpress

Gene Regulation by microRNA-16 forced expression in ErbB-2 positive murine breast cancer cells.

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