Wnt pathway-related gene expression during malignant progression in ulcerative colitis

Dekken, Herman van; Wink, Josiane C.; Vissers, Kees J.; Franken, Patrick; Schouten, W. R.; Hop, Wim C. J.; Kuipers, Ernst J.; Fodde, Riccardo; Woude, Christien J. van der

doi:10.1016/j.acthis.2007.02.007

Cited by 43 publications

(25 citation statements)

References 20 publications

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“…For example, IBD-associated colorectal tumors have lower prevalence of APC 15–17 and KRAS 18–21 mutations than sporadic tumors. Despite this, nuclear beta-catenin accumulation, a hallmark of canonical WNT signaling, is frequently found in colorectal tumors from patients with IBD 22, 23 . A similar paucity of APC mutations was reported in an animal model of IBD-associated colon cancer 24 .…”

Section: Introductionmentioning

confidence: 99%

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease−Associated Colorectal Cancers

et al. 2016

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BACKGROUND & AIMS A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer (CRC). Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. METHODS We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and CRC (15 with ulcerative colitis, 14 with Crohn’s disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the micro-dissected tumor and matched non-tumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. RESULTS Two specimens had somatic mutations in the DNA-proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with and incidence prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for non-canonical WNT signaling in development of colorectal tumors in patients with IBD. CONCLUSIONS Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and CRC.

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Section: Introductionmentioning

confidence: 99%

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease−Associated Colorectal Cancers

et al. 2016

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“…Pregnant females are susceptible to embryonic loss induced by arsenic toxicity during a relatively wide window of time in the early pregnancy (Vahter, 2007). The earliest stage of pregnancy is the preimplantation embryo stage: the time between fertilization and the implantation of the blastocyst in the uterus; during this time, the embryo passes through distinct metabolic phases, undergoing changes in the rate of protein synthesis, energy requirements, and amino acid uptake (van Dekken et al, 2007). Thus, the preimplantation embryo is very susceptible to apoptosis induced by acute exposure to arsenic in the possible mode of telomere attrition and chromosome instability (Liu et al, 2003).…”

mentioning

confidence: 99%

Intracellular redox imbalance and extracellular amino acid metabolic abnormality contribute to arsenic‐induced developmental retardation in mouse preimplantation embryos

Zhang

Liu²,

et al. 2009

Journal Cellular Physiology

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Inorganic arsenic, an environmental contaminant, is known to cause cancer, developmental retardation, and many other serious diseases. Previous researches have shown that arsenic exerts its toxicity partially through generating reactive oxygen species (ROS). However, it is still not well understood how ROS links arsenic exposure to developmental retardation of preimplantation embryo. Here we demonstrate that high-level arsenite induces severe redox imbalance by decreasing the levels of glutathione and increasing the levels of ROS through the oxidative stress adaptor p66Shc, which induces apoptosis by activating the cytochrome c-caspase. In addition, low-level arsenite seriously perturbs the metabolism of extracellular amino acid, especially that of the cytotoxic and antioxidative amino acids in preimplantation embryos, may also be the reason for developmental delay. Furthermore, an antioxidant, N-acetyl-L-cysteine, improves the development of arsenite-exposed embryos by reducing intracellular ROS and adjusting amino acid metabolism, suggesting that increasing the intracellular antioxidant level may have preventive or therapeutic effects on arsenic-induced embryonic toxicity. In conclusion, we suggest that p66Shc-linked redox imbalance and abnormal extracellular amino acid metabolism mediate arsenite-induced embryonic retardation.

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“…In the affected colon mucosa, areas of dysplasia were found to display Wnt signaling activation together with enhanced accumulation of nuclear protein cyclin D1 and reduction of membranous E-cadherin. Deregulation of the Wnt pathway, oncogene cyclin D1 and tumor suppressor E-cadherin may support the malignant degeneration of dysplastic foci in the mucosa of UC patients [83]. Another study of IBD demonstrated that TGF-β, together with IL-1 and TNF-α, can induce EMT of microvascular endothelial cells.…”

Section: Wound Healing and Other Non-tumor Conditions As Models To Elmentioning

confidence: 99%

Stroma as an Active Player in the Development of the Tumor Microenvironment

Vannucci

2014

Cancer Microenvironment

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The stroma is a considerable part of the tumor microenvironment. Because of its complexity, it can influence both cancer and immune cells in their behavior and cross-talk. Aside from soluble products released by non-cancer and cancer cells, extracellular matrix components have been increasingly recognized as more than just minor players in the constitution, development and regulation of the tumor microenvironment. The variations in the connective scaffold architecture, induced by transforming growth factor beta, lysyl oxidase and metalloproteinase activity, create different conditions of ECM density and stiffness. They exert broad effects on immune cells (e.g. physical barriers, modulation by release of stored TGF-β1), mesenchymal cells (transition to myofibroblasts), epithelial cells (epithelial-to-mesenchymal transition), cancer cells (progression to metastatic phenotype) and stem cells (activation of differentiation addressed by the microenvironment characteristics). Physiological mechanisms of the wound healing process, as well as mechanisms of fibrosis in some chronic pathologies, closely recall aspects of cancer deregulated biology. Their elucidation can provide a better understanding of tumor microenvironment immunobiology. In the following short review, we will focus on some aspects of the fibrous stroma to highlight its active participation in the tumor microenvironment constitution, tumor progression and the local immunological network.

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Wnt pathway-related gene expression during malignant progression in ulcerative colitis

Cited by 43 publications

References 20 publications

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease−Associated Colorectal Cancers

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease−Associated Colorectal Cancers

Intracellular redox imbalance and extracellular amino acid metabolic abnormality contribute to arsenic‐induced developmental retardation in mouse preimplantation embryos

Stroma as an Active Player in the Development of the Tumor Microenvironment

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