The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma

Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

doi:10.1590/s1679-45082016ao3678

Cited by 21 publications

(18 citation statements)

References 27 publications

(62 reference statements)

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“…Tunisian patients with GC had positive APC expression in 68.7%, β-catenin in 77.5% (Ayed-Guerfali et al, 2014). In the study by Bourroul et al, (2016) the immunoreactivity of the APC protein in CRC was 75% (Bourroul et al, 2016). Regarding the prognosis, overall survival time was significantly higher for patients with normal β-catenin expression alone or combined with positive APC expression.…”

Section: Discussionmentioning

confidence: 86%

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Marcolino

Pimenta

Neto

et al. 2020

Asian Pac J Cancer Prev

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Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

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Section: Discussionmentioning

confidence: 86%

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Marcolino

Pimenta

Neto

et al. 2020

Asian Pac J Cancer Prev

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“…During CRC, APC is mutated and thus becomes unable to bind with β-catenin and GSK-3β, causing an accumulation of β-catenin in the cytosol, which later translocates into the nucleus. 8 , 9 β-Catenin binds with T-cell factor (TCF)/leukocyte erythroid factor (LEF) in the nucleus and eventually transcribes downstream target genes such as C-Myc and cyclin-D1, which are responsible for cell proliferation. 7 , 10 Due to these factors, Wnt/β-catenin signaling has become the crucial target to treat CRC.…”

Section: Introductionmentioning

confidence: 99%

Vicenin-2 inhibits Wnt/β-catenin signaling and induces apoptosis in HT-29 human colon cancer cell line

Yang¹,

Zhang²,

Zhang³

et al. 2018

DDDT

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BackgroundColorectal cancer (CRC) is among highest prevailing cancers in the whole world, especially in western countries. For a diverse of reasons, patients prefer naturally occurring dietary substances over synthetic agents to prevent cancer. Vicenin-2 is largely available in a medicinal plant Ocimum sanctum and is an apigenin form, 6,8-di-C-glucoside, which has been reported to have a range of pharmacological values which includes antioxidant, hepatoprotective, anti-inflammatory and anti-cancer. This study was aimed to analyze the anti-proliferative effect of Vicenin-2 on human colon cancer cells via the Wnt/β-catenin signaling inhibition.MethodsMTT assay was used to assess the cell viability at different concentrations and time point. Vicenin-2 at a concentration of 50 µM (IC50) decreased the phosphorylated (inactive) glycogen synthase kinase-3β, cyclin D1, and non-p-β-catenin expressions in HT-29 cells, which were evidenced through western blot analysis.ResultsFurther, Vincenin-2 reduced the T-cell factor (TCF) / Leukocyte erythroid factor (LEF) reporter activity in HT-29 cells. Vicenin-2 also promoted substantial cell cycle arrest at the G2M phase of HT-29 cells, as well induced apoptosis in HT-29 cells, as revealed through flow cytometric analysis. Furthermore, immunoblot analysis showed that Vicenin-2 treatment enhanced the expression of Cytochrome C, Bax and caspase-3 whereas suppressed the Bcl-2 expression.ConclusionTogether, these results revealed that Vicenin-2 can act as a potent inhibitor of HT-29 cell proliferation and can be used as an agent against CRC.

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“…"beta-catenin destruction complex disassembly", "beta-catenin destruction complex assembly", "catenin import to nucleus"), nitric-oxide biosynthesis ("positive regulation of nitric oxide biosynthetic process", "positive regulation of nitric oxide biosynthetic process", "nitric oxide production involved in inflammatory response"), inflammasome ("positive regulation of NLRP3 inflammasome complex assembly", "pyroptosis"). The β-catenin destruction complex was recently found disrupted in colorectal cancer 67 , possibly enabling the migration of β-catenin to the nucleus and the subsequent transcription of target genes. Aberrant stabilization of the β-catenin due to mutations in the destruction complex was associated with various cancers 68 .…”

Section: Characterization Of Genes and Pathways Involved In Patients'mentioning

confidence: 99%

Network modeling of patients' biomolecular profiles for clinical phenotype/outcome prediction

Gliozzo

Perlasca

Mesiti

et al. 2020

Sci Rep

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Methods for phenotype and outcome prediction are largely based on inductive supervised models that use selected biomarkers to make predictions, without explicitly considering the functional relationships between individuals. We introduce a novel network-based approach named Patient-Net (P-Net) in which biomolecular profiles of patients are modeled in a graph-structured space that represents gene expression relationships between patients. Then a kernel-based semi-supervised transductive algorithm is applied to the graph to explore the overall topology of the graph and to predict the phenotype/clinical outcome of patients. Experimental tests involving several publicly available datasets of patients afflicted with pancreatic, breast, colon and colorectal cancer show that our proposed method is competitive with state-of-the-art supervised and semi-supervised predictive systems. Importantly, P-Net also provides interpretable models that can be easily visualized to gain clues about the relationships between patients, and to formulate hypotheses about their stratification. Phenotype and outcome prediction using sets of selected biomarkers are well-established prediction tasks in the context of computational biology, including different prediction problems ranging from the response to a specific drug 1,2 , diagnosis and prognosis 3-5 , classification of cancer subtypes 6 , outcome and recurrence prediction 7-9 and other related prediction problems 10. State-of-the-art methods for these problems are largely based on inductive supervised models that use sets of selected biomarkers, usually represented as vectors, to predict the phenotype or outcome of interest (see, e.g. 11-13), without taking into account the relationships between individuals. Several works proposed "network-based" methods by constructing graphs of patients, in order to discover the underlying structure of the data (e.g. discovery of subtypes of diseases, clinical stratification of patients) 14-17. These methods mainly used unsupervised approaches and hence have been not specifically designed and are not appropriate for phenotype/outcome prediction problems. Recently a few works proposed semi-supervised "network-based" approaches for the prediction of the phenotype/outcome of patients, on the basis of their bio-molecular profiles (e.g. gene expression of genotypic profiles) 18,19 , including also methods able to integrate multiple sources of omics data 20 , and methods based on Supervised Random Walks 21 , specifically modified for the classification of tumors 22. In this work, we introduce a novel network-based method for modeling in the "patient space". In this context the nodes of the network represent patients through an n-dimensional set of biomarker values (e.g. a set of gene expression values), and edges represent similarities between the biomarkers of a pair of patients. Hence, this "patient-space" differs from the classical "biomarker-space", where nodes represent biomarkers and edges similarities between biomarkers and not between patients 23,24...

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The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma

Cited by 21 publications

References 27 publications

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Vicenin-2 inhibits Wnt/β-catenin signaling and induces apoptosis in HT-29 human colon cancer cell line

Network modeling of patients' biomolecular profiles for clinical phenotype/outcome prediction

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The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma

Cited by 21 publications

References 27 publications

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Vicenin-2 inhibits Wnt/&beta;-catenin signaling and induces apoptosis in HT-29 human colon cancer cell line

Network modeling of patients' biomolecular profiles for clinical phenotype/outcome prediction

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Vicenin-2 inhibits Wnt/β-catenin signaling and induces apoptosis in HT-29 human colon cancer cell line