The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS
Open accessAbstract
Activating mutations in KRAS occur in 30% to 40% of colorectal cancers. How mutant KRAS alters cancer cell behavior has been studied intensively, but non-cell autonomous effects of mutant KRAS are less understood. We recently reported that exosomes isolated from mutant KRAS-expressing colon cancer cells enhanced the invasiveness of recipient cells relative to exosomes purified from wild-type KRAS-expressing cells, leading us to hypothesize mutant KRAS might affect neighboring and distant cells by regulating exosome composition and behavior. Herein, we show the results of a comprehensive proteomic analysis of exosomes from parental DLD-1 cells that contain both wild-type and G13D mutant KRAS alleles and isogenically matched derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS allele only). Mutant KRAS status dramatically affects the composition of the exosome proteome. Exosomes from mutant KRAS cells contain many tumor-promoting proteins, including KRAS, EGFR, SRC family kinases, and integrins. DKs-8 cells internalize DKO-1 exosomes, and, notably, DKO-1 exosomes transfer mutant KRAS to DKs-8 cells, leading to enhanced three-dimensional growth of these wild-type KRAS-expressing non-transformed cells. These results have important implications for non-cell autonomous effects of mutant KRAS, such as field effect and tumor progression.
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Metadata
- Authors
- Demory Beckler, M., Higginbotham, J. N., Franklin, J. L., Ham, A.-J., Halvey, P. J., Imasuen, I. E., Whitwell, C., Li, M., Liebler, D. C., & Coffey, R. J.
- Venue
- Molecular & Cellular Proteomics
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 12
- Issue
- 2
- Pages
- 343-355
- ISSN
- 1535-9476 (ISSN-L)
- OpenAlex
- W2109564400
- Cited by
- 524
- References
- 9
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Demory Beckler, M., Higginbotham, J. N., Franklin, J. L., Ham, A.-J., Halvey, P. J., Imasuen, I. E., Whitwell, C., Li, M., Liebler, D. C., & Coffey, R. J. (2013). Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS. Molecular & Cellular Proteomics. https://doi.org/10.1074/mcp.m112.022806
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