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Cited by 81Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesColorectal Cancer Treatments and Studies

Differential Reprogramming of Isogenic Colorectal Cancer Cells by Distinct Activating KRAS Mutations

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Hammond, Dean E., Mageean, Craig J., Rusilowicz, Emma V., Wickenden, Julie. A., Clague, Michael J., Prior, Ian A.·2015·Journal of Proteome Research
DOI 10.1021/pr501191aPMC PMC4356034
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Abstract

Oncogenic mutations of Ras at codons 12, 13, or 61, that render the protein constitutively active, are found in ∼16% of all cancer cases. Among the three major Ras isoforms, KRAS is the most frequently mutated isoform in cancer. Each Ras isoform and tumor type displays a distinct pattern of codon-specific mutations. In colon cancer, KRAS is typically mutated at codon 12, but a significant fraction of patients have mutations at codon 13. Clinical data suggest different outcomes and responsiveness to treatment between these two groups. To investigate the differential effects upon cell status associated with KRAS mutations we performed a quantitative analysis of the proteome and phosphoproteome of isogenic SW48 colon cancer cell lines in which one allele of the endogenous gene has been edited to harbor specific KRAS mutations (G12V, G12D, or G13D). Each mutation generates a distinct signature, with the most variability seen between G13D and the codon 12 KRAS mutants. One notable example of specific up-regulation in KRAS codon 12 mutant SW48 cells is provided by the short form of the colon cancer stem cell marker doublecortin-like Kinase 1 (DCLK1) that can be reversed by suppression of KRAS.

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    “Different KRAS alleles in CRC have distinct signatures of pathways dependency and protein expression [162].”

    From Differential Response and Resistance to KRAS-Targeted Therapy (2025) · cites this paper as [162]

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Authors
Hammond, D. E., Mageean, C. J., Rusilowicz, E. V., Wickenden, J. A., Clague, M. J., & Prior, I. A.
Affiliations
  • University of Liverpool (GB)
  • University of Liverpool , , , ,
  • Horizon Discovery (United Kingdom) (GB)
Corresponding author
  • Clague, Michael J.
  • Prior, Ian A.
ORCID
Venue
Journal of Proteome Research
Publisher
American Chemical Society (ACS)
Published
2015-01-19
Volume
14
Issue
3
Pages
1535-1546
ISSN
  • 1535-3893 (ISSN-L)
  • 1535-3907
DOI
10.1021/pr501191a
PMC
PMC4356034
OpenAlex
W1996338307
Cited by
81
References
3
Citations by year
2026: 1 · 2025: 9 · 2024: 5 · 2023: 7 · 2022: 14 · 2021: 7 · 2020: 9 · 2019: 10 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 3
FWCI
2.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Proteome Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust (WT089137)
  • European Research Council (259015)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords
KRAS mutation, colorectal cancer, codon 12 mutation, codon 13 mutation, G12V, G12D, isogenic cell lines, SW48 cells, proteome, phosphoproteome, DCLK1, cancer stem cells, oncogenic Ras, tumor cell reprogramming
MeSH terms
Doublecortin-Like Kinases, Humans, Mutation, Genes, ras, Colorectal Neoplasms, Up-Regulation, Protein Serine-Threonine Kinases, Proteomics, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins

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