Li, J., Sordella, R., Powers, S. (June 2016) Effectors and potential targets selectively upregulated in human KRAS-mutant lung adenocarcinomas. Sci Rep, 6. p. 27891. ISSN 2045-2322 (Electronic)2045-2322 (Linking)
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Abstract
Genetic and proteomic analysis of human tumor samples can provide an important compliment to information obtained from model systems. Here we examined protein and gene expression from the Cancer Genome and Proteome Atlases (TCGA and TCPA) to characterize proteins and protein-coding genes that are selectively upregulated in KRAS-mutant lung adenocarcinomas. Phosphoprotein activation of several MAPK signaling components was considerably stronger in KRAS-mutants than any other group of tumors, even those with activating mutations in receptor tyrosine kinases (RTKs) and BRAF. Co-occurring mutations in KRAS-mutants were associated with differential activation of PDK1 and PKC-alpha. Genes showing strong activation in RNA-seq data included negative regulators of RTK/RAF/MAPK signaling along with potential oncogenic effectors including activators of Rac and Rho proteins and the receptor protein-tyrosine phosphatase genes PTPRM and PTPRE. These results corroborate RAF/MAPK signaling as an important therapeutic target in KRAS-mutant lung adenocarcinomas and pinpoint new potential targets.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > KRAS diseases & disorders > cancer > cancer types > lung cancer |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Cancer Genetics CSHL Cancer Center Program > Signal Transduction CSHL labs > Powers lab CSHL labs > Sordella lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Cellular Communication in Cancer Program |
| Depositing User: | Matt Covey |
| Date: | 15 June 2016 |
| Date Deposited: | 23 Jun 2016 18:45 |
| Last Modified: | 26 Oct 2020 17:02 |
| PMCID: | PMC4908391 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/32875 |
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