Quantitative Phosphoproteomics Reveals a Cluster of Tyrosine Kinases That Mediates Src Invasive Activity in Advanced Colon Carcinoma Cells
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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”
From The molecular rationale of Src inhibition in colorectal carcinomas (2014) · cites this paper as [15]
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Cites
The protein kinase complement of the human genome
Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145 · see citing works
Met, metastasis, motility and more
Birchmeier, C., Birchmeier, W., Gherardi, E., & Woude, G. V. (2003) · Nature reviews. Molecular cell biology · doi:10.1038/nrm1261 · Cited by 2,667 · see citing works
Cellular functions regulated by Src family kinases.
Thomas, S. M., & Brugge, J. (1997) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.13.1.513 · Cited by 2,610 · see citing works
Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317 · see citing works
Integrin-regulated FAK–Src signaling in normal and cancer cells
Mitra, S. K., & Schlaepfer, D. D. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.08.011 · Cited by 1,591 · see citing works
Sahai, E. A., & Marshall, C. J. (2003) · Nature Cell Biology · doi:10.1038/ncb1019 · Cited by 1,148 · see citing works
Yeatman, T. J. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1366 · Cited by 1,113 · see citing works
Ponzetto, C., Bardelli, A., Zhen, Z., Maina, F., Zonca, P. D., Giordano, S., Graziani, A., Panayotou, G., & Comoglio, P. M. (1994) · Cell · doi:10.1016/0092-8674(94)90318-2 · Cited by 994 · see citing works
Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies
Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., et al. (2007) · Science · doi:10.1126/science.1142946 · Cited by 938 · see citing works
Src family kinases in tumor progression and metastasis
Summy, J. M., & Gallick, G. E. (2003) · Cancer and Metastasis Reviews · doi:10.1023/a:1023772912750 · Cited by 827 · see citing works
Activating SRC mutation in a subset of advanced human colon cancers
Irby, R. B., Mao, W., Coppola, D., Kang, J., Loubeau, J. M., Trudeau, W., Karl, R., Fujita, D. J., Jove, R., & Yeatman, T. J. (1999) · Nature Genetics · doi:10.1038/5971 · Cited by 489 · see citing works
Assembly and biological role of podosomes and invadopodia
Gimona, M., Buccione, R., Courtneidge, S. A., & Linder, S. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.01.005 · Cited by 404 · see citing works
The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells
Coopman, P. J., Do, M. T. H., Barth, M. M., Bowden, E. T., Hayes, A. J., Basyuk, E. I., Blancato, J. K., Vezza, P. R., McLeskey, S. W., Mangeat, P. H., et al. (2000) · Nature · doi:10.1038/35021086 · Cited by 324 · see citing works
Roche, S., Koegl, M., & Courtneidge, S. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.9185 · Cited by 267 · see citing works
Self-citationDisanza, A., Mantoani, S., Hertzog, M., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1502 · Cited by 253 · see citing works
Roche, S., Koegl, M., Barone, M. V., Roussel, M. F., & Courtneidge, S. A. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.2.1102 · Cited by 244 · see citing works
Self-citationThe ERBB3 receptor in cancer and cancer gene therapy
Sithanandam, G., & Anderson, L. M. (2008) · Cancer Gene Therapy · doi:10.1038/cgt.2008.15 · Cited by 240 · see citing works
Mechanisms of COPII vesicle formation and protein sorting
Sato, K., & Nakano, A. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.091 · Cited by 235 · see citing works
BindingDB (2025) · PubMed · doi:10.7270/q2dv1qm3 · Cited by 235 · see citing works
Phosphoproteomic analysis of Her2/neu signaling and inhibition
Bose, R., Molina, H., Patterson, A., Bitok, J. K., Periaswamy, B., Bader, J. S., Pandey, A., & Cole, P. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603948103 · Cited by 215 · see citing works
Yamamoto, N., Takeshita, K., Shichijo, M., Kokubo, T., Satô, M., Nakashima, K., Ishimori, M., Nagai, H., Li, Y.-F., Yura, T., et al. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.052316 · Cited by 190 · see citing works
Phosphoproteomic approaches to elucidate cellular signaling networks
Schmelzle, K., & White, F. M. (2006) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2006.06.004 · Cited by 155 · see citing works
Eph–ephrin signalling in adult tissues and cancer
Merlos‐Suárez, A., & Batlle, E. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.01.011 · Cited by 137 · see citing works
Roche, S., McGlade, J. C., Jones, M., et al. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00874.x · Cited by 137 · see citing works
Self-citationEzrin has properties to self-associate at the plasma membrane
Andréoli, C., Martin, M., Borgne, R. L., Reggio, H., & Mangeat, P. H. (1994) · Journal of Cell Science · doi:10.1242/jcs.107.9.2509 · Cited by 134 · see citing works
Overexpression of EPHA2 receptor destabilizes adherens junctions via a RhoA-dependent mechanism
Fang, W. B., Ireton, R. C., Zhuang, G., et al. (2008) · Journal of Cell Science · doi:10.1242/jcs.017145 · Cited by 129 · see citing works
Amanchy, R., Kalume, D. E., Iwahori, A., Zhong, J., & Pandey, A. (2005) · Journal of Proteome Research · doi:10.1021/pr050134h · Cited by 125 · see citing works
CUB Domain-Containing Protein 1 Is a Novel Regulator of Anoikis Resistance in Lung Adenocarcinoma
Uekita, T., Jia, L., Narisawa‐Saito, M., Yokota, J., Kiyono, T., & Sakai, R. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01246-07 · Cited by 119 · see citing works
Laird, A., Li, G., Moss, K. G., Blake, R. A., Broome, M. A., Cherrington, J. M., & Mendel, D. B. (2003) · PubMed · Cited by 101 · see citing works
Global Impact of Oncogenic Src on a Phosphotyrosine Proteome
Luo, W., Slebos, R. J. C., Hill, S., Li, M., Brábek, J., Amanchy, R., Chaerkady, R., Pandey, A., Ham, A. L., & Hanks, S. K. (2008) · Journal of Proteome Research · doi:10.1021/pr800187n · Cited by 99 · see citing works
Pragmin, a Novel Effector of Rnd2 GTPase, Stimulates RhoA Activity
Tanaka, H., Katoh, H., & Negishi, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511314200 · Cited by 92 · see citing works
Luangdilok, S., Box, C., Patterson, L., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0331 · Cited by 89 · see citing works
Iwaya, K., Oikawa, K., Semba, S., Tsuchiya, B., Mukai, Y., Otsubo, T., Nagao, T., Izumi, M., Kuroda, M., Domoto, H., et al. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00488.x · Cited by 82 · see citing works
VHS domain – a longshoreman of vesicle lines
Lohi, O., Poussu, A. M., Mao, Y., Quiocho, F. A., & Lehto, V.-P. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03287-2 · Cited by 78 · see citing works
The Human p62 cDNA Encodes Sam68 and Not the RasGAP-Associated p62 Protein
Lock, P., Fumagalli, S., Polakis, P. G., McCormick, F., & Courtneidge, S. A. (1996) · Cell · doi:10.1016/s0092-8674(00)80989-7 · Cited by 72 · see citing works
Sirvent, A., Boureux, A., Simon, V., Leroy, C., & Roche, S. (2007) · Oncogene · doi:10.1038/sj.onc.1210543 · Cited by 68 · see citing works
Self-citationI, S. T. T., Nie, Z., Stewart, A. L., et al. (2004) · Journal of Cell Science · doi:10.1242/jcs.01526 · Cited by 61 · see citing works
SRC transcriptional activation in a subset of human colon cancer cell lines
Dehm, S. M., Senger, M.-A., & Bonham, K. (2001) · FEBS Letters · doi:10.1016/s0014-5793(00)02354-1 · Cited by 54 · see citing works
Pandey, A., Blagoev, B., Kratchmarova, I., Fernandez, M. M., Nielsen, M. M., Kristiansen, T. Z., Ohara, O., Podtelejnikov, A. V., Roche, S., Lodish, H. F., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205988 · Cited by 50 · see citing works
Self-citationEmaduddin, M., Bicknell, D. C., Bodmer, W. F., & Feller, S. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712176105 · Cited by 50 · see citing works
Liang, X., Hajivandi, M., Veach, D. R., Wisniewski, D. J., Clarkson, B. D., Resh, M. D., & Pope, R. M. (2006) · PROTEOMICS · doi:10.1002/pmic.200600109 · Cited by 49 · see citing works
Franco, M., Furstoss, O., Simon, V., Benistant, C., Hong, W. J., & Roche, S. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.5.1932-1947.2006 · Cited by 47 · see citing works
Self-citationGiuriato, S., Bodin, S., Erneux, C., Woscholski, R., Plantavid, M. M., Chap, H., & Payrastre, B. (2000) · Biochemical Journal · doi:10.1042/bj3480107 · Cited by 28 · see citing works
Giuriato, S., Bodin, S., Erneux, C., Woscholski, R., Plantavid, M. M., Chap, H., & Payrastre, B. (2000) · PubMed Central · Cited by 23 · see citing works
Represa, A., Trabelsi-Terzidis, H., Plantier, M., et al. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1383 · Cited by 22 · see citing works
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HATAKEYAMA, M. (2017) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.93.013 · Cited by 261 · see citing works
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Jin, W. (2020) · Cancers · doi:10.3390/cancers12051339 · Cited by 86 · see citing works
Sirvent, A., Bénistant, C., Pannequin, J., Veracini, L., Simon, V, Bourgaux, J.-F., Hollande, F., Cruzalegui, F., & Roche, S. (2010) · Oncogene · doi:10.1038/onc.2009.450 · Cited by 69 · see citing works
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Gargalionis, A. N., Karamouzis, M. V., & Papavassiliou, A. G. (2014) · International Journal of Cancer · doi:10.1002/ijc.28299 · Cited by 47 · see citing works
Sirvent, A., Vigy, O., Orsetti, B., Urbach, S., & Roche, S. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.018168 · Cited by 33 · see citing works
Self-citationChen, P.-H., Peng, C.-Y., Pai, H.-C., Teng, C.-M., Chen, C.-C., & Yang, C.-R. (2011) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.06.004 · Cited by 28 · see citing works
- 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
- bronze
- doi.org
- 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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