Prognostic relevance of Src activation in stage II-III colon cancer

Martínez-Pérez, Julia; Lopez-Calderero, Iker; Sáez, Carmen; Benavent, Marta; Limón, María Luisa; Gonzalez-Exposito, Reyes; Soldevilla, Beatriz; Riesco-Martinez, M.C.; Salamanca, Javier; Carnero, Amancio; Garcia-Carbonero, Rocío

doi:10.1016/j.humpath.2017.05.025

Cited by 15 publications

(8 citation statements)

References 17 publications

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“…Consistently, SFKs are frequently deregulated in CRC (80%) and their level of aberrant activity has been associated with poor prognosis [ 49 , 50 , 51 ]. Notably, SFKs are activated in intestinal polyps and adenoma [ 26 , 52 ] and SFK activity level is a prognostic factor of disease-free survival and overall survival in patients with early stage II-III CRC [ 53 ]. Active membrane localised FGR and HCK have been associated with prognosis and local inflammatory response, possibly by decreasing cytotoxic T lymphocytes in patients with stage I-III CRC [ 54 ].…”

Section: Sfks In Human Crcmentioning

confidence: 99%

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

Sirvent

Mevizou

Naim

et al. 2020

Cancers

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Src, originally identified as an oncogene, is a membrane-anchored tyrosine kinase and the Src family kinase (SFK) prototype. SFKs regulate the signalling induced by a wide range of cell surface receptors leading to epithelial cell growth and adhesion. In the intestine, the SFK members Src, Fyn and Yes regulate epithelial cell proliferation and migration during tissue regeneration and transformation, thus implicating conserved and specific functions. In patients with colon cancer, SFK activity is a marker of poor clinical prognosis and a potent driver of metastasis formation. These tumorigenic activities are linked to SFK capacity to promote the dissemination and tumour-initiating capacities of epithelial tumour cells. However, it is unclear how SFKs promote colon tumour formation and metastatic progression because SFK-encoding genes are unfrequently mutated in human cancer. Here, we review recent findings on SFK signalling during intestinal homeostasis, regeneration and tumorigenesis. We also describe the key nongenetic mechanisms underlying SFK tumour activities in colorectal cancer, and discuss how these mechanisms could be exploited in therapeutic strategies to target SFK signalling in metastatic colon cancer.

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Section: Sfks In Human Crcmentioning

confidence: 99%

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

Sirvent

Mevizou

Naim

et al. 2020

Cancers

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“…It also influences the survival of CRC patients. Therefore, inhibition of SRC may have an important therapeutic effect in CRC, and many studies are currently underway [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer

et al. 2022

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Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell–cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC.

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“…SRC, the first proto-oncogene found, encodes a cytoplasmic tyrosine kinase that belongs to Src family kinases, which were found to play a key role in the growth, differentiation, proliferation, invasion, and metastasis of tumor cells [26]. A cohort study demonstrated that higher mRNA expression of Src was related to poor prognosis in early-stage colon cancer and had a stronger negative impact on outcome in LCC and stage II disease [27]. Several studies have found a more favorable survival adjusted for tumor stage in LCC [28][29][30], whereas Weiss et al indicated that RCC in stage Ⅰ-II disease demonstrated a better overall survival compared to LCC [31], which might be related to the expression of SRC was higher in early-stage LCC.…”

Section: Discussionmentioning

confidence: 99%

Analysis of differential gene expression between right-sided and left-sided colon cancer by bioinformatics analysis

Chi

Chen

2020

Preprint

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Background Colon cancer is a common tumor of the digestive tract worldwide. Recent researches have revealed that colon cancer exhibits distinct differences in clinical and biological characteristics depending on the location of the tumor. However, the underlying genetic and molecular mechanism of the differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) are not fully understood. This study aimed to identify molecular potential biomarkers and therapeutic targets for precise treatment of right-sided and left-sided colon cancer using bioinformatics analysis. Methods The gene microarray profile, named GSE44076, from the Gene Expression Omnibus (GEO) public database was downloaded and processed to then select differentially expressed genes (DEGs) on the base of two sample groups of RCC and LCC. Also, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein–protein interaction (PPI) network construction, module analysis, validation of hub genes, and survival analysis. Results Finally, we obtained 2259 DEGs between RCC and LCC, 1300 of which were upregulated in RCC and 945 of which were upregulated in LCC. The results of GO and KEGG analysis of the DEGs indicated that the biological functions of DEGs in RCC and LCC were significantly different. CTLA4, IL10, IL2RB, IFNG, NCAM1, EGFR, MYC, SRC, CUL3, and NCBP2 were identified from the PPI networks as the hub genes of RCC and LCC. Among the hub genes, the log-rank tests for overall survival (OS) and disease free survival (DFS) were applied. Moreover, all hub genes, except CUL3, had differential expression levels of miRNA between tumor group and normal group. Conclusion These hub genes and pathways identified based on bioinformatics analysis might conduce to explain the differences between RCC and LCC, and most of the hub genes were specific to the malignant tissues. Notably, these hub genes, especially the genes associated with immunotherapy such as CTLA4, might be potential specific targets or prognostic markers for precise treatment of colon cancer.

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Prognostic relevance of Src activation in stage II-III colon cancer

Cited by 15 publications

References 17 publications

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer

Analysis of differential gene expression between right-sided and left-sided colon cancer by bioinformatics analysis

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