scholarly journals Epithelial-Mesenchymal Transition Phenotype, Metformin, and Survival for Colorectal Cancer Patients with Diabetes Mellitus II

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yaodu Wang ◽  
Zhiyang Wu ◽  
Likuan Hu
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Multivariate Regression Analysis ◽  
Stage I ◽  
Clinicopathological Parameters ◽  
Mesenchymal Transition ◽  
Patients With Diabetes ◽  
E Cadherin

Objectives. We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice. Methods. We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0. Results. In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin (P=0.014) and less vimentin (P=0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 (P=0.048, P=0.009), tumor invasive depth (T) (P<0.001, P=0.045), and lymph invasion (N) (P=0.013, P=0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P=0.038) and metformin use (P=0.015P=0.044) and lymph invasion (P=0.016P=0.023) were considered as the prognostic factors for both DFS and overall survival (OS). Conclusion. Our study suggested that metformin may impede the EMT process and improve survival for stage I–III CRC patients with DM II.

The Emerging Role of Metformin in the Prevention and Treatment of Colorectal Cancer: A Game Changer for Management of Colorectal Cancer

2021 ◽  
Vol 18 ◽  
Author(s):  
Moein Ala
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Inflammation ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapeutic Agents ◽  
Advanced Adenoma ◽  
High Risk Population ◽  
Mesenchymal Transition ◽  
Cytotoxicity Activity ◽  
Increased Risk ◽  
Patients With Diabetes

: Metformin is an old, inexpensive and relatively safe anti-diabetic medication which can decrease the increased risk of several types of cancer in patients with diabetes. Recent meta-analyses revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cell cytotoxicity activity. It was uncovered that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreased the incidence of colonic adenoma in patients with acromegaly and reduced the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreased the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population.

scholarly journals Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽  
2015 ◽  
Vol 35 (24) ◽  
pp. 3151-3162 ◽  
Author(s):  
Q Zhang ◽  
T Wei ◽  
K Shim ◽  
K Wright ◽  
K Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

Epithelial–mesenchymal transition and cancer stem cell interactions in breast phyllodes tumours: immunohistochemical evaluation of EZH2, EZR, HMGA2, CD24 and CD44 in correlation with outcome analysis

2021 ◽  
pp. jclinpath-2020-207068
Author(s):  
Syed Salahuddin Ahmed ◽  
Jeffrey Chun Tatt Lim ◽  
Aye Aye Thike ◽  
Jabed Iqbal ◽  
Puay Hoon Tan
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumour Progression ◽  
High Mobility ◽  
Disease Free Survival ◽  
Clinicopathological Parameters ◽  
Outcome Analysis ◽  
Mesenchymal Transition ◽  
Associated Proteins ◽  
Phyllodes Tumours

AimPhyllodes tumours (PTs) categorised as benign, borderline and malignant, account for 1% of all breast tumours. Histological assessment does not always predict tumour behaviour, hindering determination of the clinical course and management.Epithelial–mesenchymal transition (EMT) is an important process during embryogenesis. Dysregulation of EMT causes loss of cell polarity, decreased intercellular adhesion, increased motility and invasiveness, promoting tumour progression. Similarly, cancer stem cells (CSCs) promote tumour growth, resistance and recurrence. The aim of this study is to evaluate expression of CSC markers; enhancer of zeste homolog 2 (EZH2), CD24 and CD44 and EMT associated proteins; ezrin (EZR) and high-mobility group AT-hook 2 (HMGA2) in PTs.MethodUing tissue microarray sections, immunohistochemistry was performed on 360 PTs. Epithelial and stromal expressions of EZH2, EZR, HMGA2, CD24 and CD44 were evaluated to assess their impact on disease progression and behaviour in correlation with clinicopathological parameters.ResultsStromal expression of EZH2, EZR and HMGA2 was observed in 73 (20.3%), 53 (14.7%) and 28 (7.8%) of tumours, epithelial expression in 121 (35.9%), 3 (0.8%) and 351 (97.5%) tumours, respectively. CD24 and CD44 staining was absent in both components.ConclusionExpression of biomarkers correlated significantly with aggressive tumour traits such as stromal hypercellularity, atypia, mitoses and permeative tumour borders.Stromal expression of EZH2 and EZR shortened disease-free survival and overall survival; HMGA2 expression did not alter patient survival. EZH2 and EZR may thus be useful in predicting PT behaviour.

scholarly journals Correlation between FAK and EGF-Induced EMT in Colorectal Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Kun Huang ◽  
Ningning Gao ◽  
Donglin Bian ◽  
Qixi Zhai ◽  
Puxu Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Egfr Signaling Pathway ◽  
Colorectal Cancer Cells ◽  
E Cadherin

Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of colorectal cancer, which is mediated by FAK and EGF. However, whether FAK participates in EMT in colorectal cancer cells through the EGF/EGFR signaling pathway remains unknown. The aim of this study was to investigate the effector mechanisms of FAK in the process of EGF-induced EMT in colorectal cancer cells and to determine whether miR-217 is involved in this process. Caco-2 cancer cells were routinely cultured with and without treatment with 100 ng/mL EGF, and changes in cell morphology were observed using an inverted microscope. In addition, a transwell assay was used to detect cell migration under the condition of EGF treatment. The expression of FAK, pFAK, E-cadherin, vimentin, and β actin was assessed by western blotting, and the expression of miR-217 was assessed using real-time PCR. We found that EGF induced EMT in colorectal cancer cells and enhanced cell migration and invasion ability. Moreover, FAK was involved in the EGF-induced EMT of colorectal cancer cells. EGF upregulated the expression of E-cadherin in colorectal cancer cells by activating FAK, and miR-217 was found to participate in EGF-induced EMT in colorectal cancer cells. Our findings indicate that EGF induces EMT in colorectal cancer cells by activating FAK, and miR-217 is involved in the EGF/FAK/E-cadherin signaling pathway.

Elevated soluble E-cadherin during the epithelial-mesenchymal transition process and as a diagnostic marker in colorectal cancer

Gene ◽  
2020 ◽  
Vol 754 ◽  
pp. 144899
Author(s):  
Shuzhen Zhu ◽  
Guanghui Zhao ◽  
Xiaoyun Zhao ◽  
Xiaohong Zhan ◽  
Meijuan Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Diagnostic Marker ◽  
Transition Process ◽  
Mesenchymal Transition ◽  
E Cadherin

The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer

2016 ◽  
Vol 70 (4) ◽  
pp. 331-356 ◽  
Author(s):  
Anelisa Jaca ◽  
Padmini Govender ◽  
Michael Locketz ◽  
Richard Naidoo
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Clinicopathological Features ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Sporadic Cases ◽  
E Cadherin

AimsThe study was conducted to assess the expression levels of epithelial mesenchymal transition (EMT) proteins (E-cadherin, N-cadherin, snail-1 and vimentin) and miRNA-21. In addition, we correlated these data with clinicopathological features in Colorectal cancer.MethodsH&E slides from a total of 59 formalin fixed paraffin embedded tissue blocks were examined by a pathologist to demarcate normal and tumour regions. Immunohistochemical analysis of mismatch repair proteins (MLH1, MSH2 and MSH6) and EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) was performed. The miRNA-21 expression levels were determined using qRT-PCR and the data was analysed using the relative quantification method. The Fisher's exact and Pearson's χ2 tests were used to correlate snail-1, E-cadherin, miRNA-21 and clinicopathological data.ResultsOur results showed a statistically significant correlation between high miRNA-21 expression levels and E-cadherin positive cases. There was also an association between high miRNA-21 expression levels and negative snail-1 expression. No significant correlation was seen between miRNA-21 expression levels and clinicopathological features. Moreover, high expression levels of miRNA-21 were significantly associated with the sporadic cases.ConclusionsOur data suggest that miRNA-21 in association with E-cadherin and snail-1 does not play a significant role in the development and progression of this disease.

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