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Activation of Src kinase in primary colorectal carcinoma: An indicator of poor clinical prognosis
Open accessAbstract
BACKGROUND: The specific activity of the non‐receptor protein tyrosine kinase, Src, is increased in the majority of colon and rectal adenocarcinomas compared to normal mucosa. However, the prognostic significance of this difference is unknown. The objective of the current study was to determine if Src activity is a marker for poor clinical prognosis in colon carcinoma patients. As Src activation leads to expression of urokinase/plasminogen activator receptor (u‐PAR), expression of Src and u‐PAR were correlated with patient survival. METHODS: Tumors and adjacent normal colonic mucosae from 45 patients with colorectal carcinoma were screened for Src activity by the immune complex kinase assay. Expression of u‐PAR was determined by enzyme linked immunoabsorbent assay. The primary tumor‐to‐normal mucosa ratios of activity were compared following classification and regression tree (CART) analysis to determine the prognostic significance of elevated specific Src activity. Expression of u‐PAR was correlated with Src activity. RESULTS: By CART analysis, Src activity in tumors elevated more than twofold over normal mucosa was significant. Increased Src activity significantly correlated with Dukes stage, pT and pN classification, and increased u‐PAR levels (P < 0.001). Kaplan Meier analysis showed a significant association between elevated Src activity and shorter overall survival of all patients (P = 0.0004) and of Dukes Stage A‐C patients (P = 0.0037). In patients who underwent curative resection, a significant correlation with a decreased disease‐free survival rate was found (P < 0.0001). Multivariate analysis revealed that elevated Src activity was a prognostic parameter independent of M classification (P = 0.0125, relative risk 3.54, 95% confidence interval 1.31 – 9.76). CONCLUSIONS: Src activity is an independent indicator of poor clinical prognosis in all stages of human colon carcinoma. These data suggest that Src‐specific inhibitors may have a therapeutic role in inhibiting tumor progression and metastasis, and that measurement of Src activity may aid in selection of early stage patients for adjuvant therapy. Cancer 2002;94:344–51. © 2002 American Cancer Society.
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“In addition to SFK activity and CRC progression, SFK activity has been reported as a marker of poor clinical prognosis (Aligayer et al., 2002).”
From Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab (2011) · cites this paper as Aligayer et al., 2002
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“Moreover, aberrant SRC activation has been associated with a more aggressive phenotype and a worse prognosis in CRC patients [27, 28].”
From Co-targeting SRC overcomes resistance to BRAF inhibitors in colorectal cancer (2025) · cites this paper as [28]
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“Aberrant SRC activation has been associated with a more aggressive phenotype and a worse prognosis in CRC patients [27, 28, 39].”
From Co-targeting SRC overcomes resistance to BRAF inhibitors in colorectal cancer (2025) · cites this paper as [28]
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“and increased c-Src levels correlate with worse patient survival [13].”
From Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src (2016) · cites this paper as [13]
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“c-src high activity was proved to be correlated with dismal survival, emerging as an independent aggravating prognostic factor.14”
From The molecular rationale of Src inhibition in colorectal carcinomas (2014) · cites this paper as [14]
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Metadata
- Authors
- Allgayer, H., Boyd, D. D., Heiss, M. M., Abdalla, E. K., Curley, S. A., & Gallick, G. E.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Gallick, Gary E.
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2002-01-15
- Volume
- 94
- Issue
- 2
- Pages
- 344-351
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- OpenAlex
- W1532635242
- Cited by
- 251
- References
- 51
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 11 · 2018: 7 · 2017: 9 · 2016: 11 · 2015: 14 · 2014: 16 · 2013: 16 · 2012: 13
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gillson Longenbaugh Foundation
- Deutsche Krebshilfe
- National Institutes of Health (5r01ca065527-07)
- National Cancer Institute (CA65527, CA69926, CA53617, CA 58311)
- National Institute of Dental and Craniofacial Research (DE10845, R01DE010845)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- Src kinase, colorectal cancer, prognostic factors, urokinase-type plasminogen activator receptor, non-receptor tyrosine kinase, overall survival, disease-free survival, Dukes stage, adjuvant therapy selection, Src kinase inhibitor, metastasis
- MeSH terms
- CSK Tyrosine-Protein Kinase, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Enzyme Activation, Female, Humans, Male, Middle Aged, Mucous Membrane, Protein-Tyrosine Kinases, Receptors, Cell Surface, Colorectal Neoplasms, Survival Rate, src Homology Domains, src-Family Kinases, Receptors, Urokinase Plasminogen Activator
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