Cited by 114Protein Kinase Regulation and GTPase SignalingCancer Mechanisms and TherapyAdvanced Proteomics Techniques and Applications

Quantitative Phosphoproteomics Reveals a Cluster of Tyrosine Kinases That Mediates Src Invasive Activity in Advanced Colon Carcinoma Cells

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Leroy, Cédric, Fialin, Camille, Sirvent, Audrey, Simon, Valérie, Urbach, Serge, Poncet, Joël, Robert, Bruno, Jouin, Patrick +1 more·2009·Cancer Research

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Abstract

The nonreceptor tyrosine kinase Src is frequently overexpressed and/or activated in human colorectal carcinoma (CRC), and its increased activity has been associated with a poor clinical outcome. Src has been implicated in growth and invasion of these cancer cells by still not well-known mechanisms. Here, we addressed Src oncogenic signaling using quantitative phosphoproteomics. Src overexpression increased growth and invasiveness of metastatic SW620 CRC cells. Stable isotope labeling with amino acids in cell culture in combination with liquid chromatography tandem mass spectrometry allowed the identification of 136 proteins which exhibited a significant increase in and/or association with tyrosine phosphorylation upon Src expression. These mainly include signaling, cytoskeleton, and vesicular-associated proteins. Interestingly, Src also phosphorylated a cluster of tyrosine kinases, i.e., the receptors Met and EphA2, the cytoplasmic tyrosine kinase Fak, and pseudo-tyrosine kinase SgK223, which were required for its invasive activity. Similar results were obtained with metastatic Colo205 CRC cells that exhibit high endogenous Src activity. We concluded that Src uses a tyrosine kinases network to promote its invasive activity in CRC and this implicates a reverse signaling via tyrosine kinase receptors. Targeting these tyrosine kinases may be of significant therapeutic value in this cancer. [Cancer Res 2009;69(6):2279–86]

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  • Src overexpression in metastatic CRC cell lines promotes tumor growth in vitro and in vivo, mainly through elevation of tyrosine phosphorylation.

    “Src overexpression in metastatic CRC cell lines also seems to promote tumor growth both in vitro and in vivo targeting distinct protein substrates, respectively, mainly through elevation of tyrosine phosphorylation.15,16”

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Authors
Leroy, C., Fialin, C., Sirvent, A., Simon, V., Urbach, S., Poncet, J., Robert, B., Jouin, P., & Roche, S.
Affiliations
  • 1Centre National de la Recherche Scientifique UMR5237, University of Montpellier 1 and 2, CRBM,
  • Centre National de la Recherche Scientifique (FR)
  • Inserm (FR)
  • 2UMR 5203 Institut National de la Santé et de la Recherche Médicale U661, University of Montpellier 1 and 2, IGF, and
Venue
Cancer Research
Published
2009-03-15
Volume
69
Issue
6
Pages
2279-2286
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2003380134
Cited by
114
References
45
Citations by year
2026: 4 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 7 · 2021: 10 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 11 · 2016: 4 · 2015: 5 · 2014: 10 · 2013: 5 · 2012: 8
FWCI
4.56
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Ligue Contre le Cancer
  • Centre National de la Recherche Scientifique (10/09)
  • Institut National Du Cancer
  • Université de Montpellier
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
Src kinase, colorectal cancer, tumor invasion, tyrosine kinase signaling, c-Met, EphA2, focal adhesion kinase, reverse signaling, tyrosine phosphorylation, metastasis, SW620 cells, COLO 205 cells, therapeutic target
MeSH terms
Animals, Colonic Neoplasms, Humans, Mice, Nude, Neoplasm Invasiveness, Phosphorylation, Protein-Tyrosine Kinases, Transplantation, Heterologous, Signal Transduction, src-Family Kinases, Proteomics, Cell Line, Tumor, Cell Growth Processes, Mice

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