scholarly journals Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-α induced epithelial-to-mesenchymal transition in colorectal cancer

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Lanlan Huang ◽  
Xiaoyan Wang ◽  
Chuangyu Wen ◽  
Xiangling Yang ◽  
Minmin Song ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tnf Α ◽  
Lymph Metastasis

scholarly journals Resveratrol Chemosensitizes TNF-β-Induced Survival of 5-FU-Treated Colorectal Cancer Cells

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 888 ◽  
Author(s):  
Constanze Buhrmann ◽  
Mina Yazdi ◽  
Bastian Popper ◽  
Parviz Shayan ◽  
Ajay Goel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tnf Α ◽  
Colorectal Cancer Cells ◽  
Carcinogenic Effects ◽  
Underlying Mechanisms ◽  
Lymphotoxin Α ◽  
First Time

Objective: Resveratrol, a safe and multitargeted natural agent, has been linked with inhibition of survival and invasion of tumor cells. Tumor Necrosis Factor-β (TNF-β) (Lymphotoxin α) is known as an inflammatory cytokine, however, the underlying mechanisms for its pro-carcinogenic effects and whether resveratrol can suppress these effects in the tumor microenvironment are poorly understood. Methods: We investigated whether resveratrol modulates the effects of 5-Fluorouracil (5-FU) and TNF-β on the malignant potential of human colorectal cancer (CRC) cells (HCT116) and their corresponding isogenic 5-FU-chemoresistant derived clones (HCT116R) in 3D-alginate tumor microenvironment. Results: CRC cells cultured in alginate were able to migrate from alginate and the numbers of migrated cells were significantly increased in the presence of TNF-β, similar to TNF-α, and dramatically decreased by resveratrol. We found that TNF-β promoted chemoresistance in CRC cells to 5-FU compared to control cultures and resveratrol chemosensitizes TNF-β-induced increased capacity for survival and invasion of HCT116 and HCT116R cells to 5-FU. Furthermore, TNF-β induced a more pronounced cancer stem cell-like (CSC) phenotype (CD133, CD44, ALDH1) and resveratrol suppressed formation of CSC cells in two different CRC cells and this was accompanied with a significant increase in apoptosis (caspase-3). It is noteworthy that resveratrol strongly suppressed TNF-β-induced activation of tumor-promoting factors (NF-κB, MMP-9, CXCR4) and epithelial-to-mesenchymal-transition-factors (increased vimentin and slug, decreased E-cadherin) in CRC cells. Conclusion: Our results clearly demonstrate for the first time that resveratrol modulates the TNF-β signaling pathway, induces apoptosis, suppresses NF-κB activation, epithelial-to-mesenchymal-transition (EMT), CSCs formation and chemosensitizes CRC cells to 5-FU in a tumor microenvironment.

scholarly journals Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer

2021 ◽  
Vol 38 (2) ◽  
Author(s):  
Wenqian Zheng ◽  
Jinhui Hu ◽  
Yiming Lv ◽  
Bingjun Bai ◽  
Lina Shan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

AbstractThe use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.

scholarly journals Lessons to Learn for Adequate Targeted Therapy Development in Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 22 (9) ◽  
pp. 5019
Author(s):  
Helena Oliveres ◽  
David Pesántez ◽  
Joan Maurel
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Tyrosine Kinases ◽  
Epithelial To Mesenchymal Transition ◽  
Acquired Resistance ◽  
Post Translational Modification ◽  
Mesenchymal Transition ◽  
Igf1r Signaling ◽  
Colorectal Cancer Patients

Insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase that regulates cell growth and proliferation. Upregulation of the IGF1R pathway constitutes a common paradigm shared with other receptor tyrosine kinases such as EGFR, HER2, and MET in different cancer types, including colon cancer. The main IGF1R signaling pathways are PI3K-AKT and MAPK-MEK. However, different processes, such as post-translational modification (SUMOylation), epithelial-to-mesenchymal transition (EMT), and microenvironment complexity, can also contribute to intrinsic and acquired resistance. Here, we discuss new strategies for adequate drug development in metastatic colorectal cancer patients.

scholarly journals Epithelial–Mesenchymal Transition (EMT) Induced by TNF-α Requires AKT/GSK-3β-Mediated Stabilization of Snail in Colorectal Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56664 ◽  
Author(s):  
Hao Wang ◽  
Hong-Sheng Wang ◽  
Bin-Hua Zhou ◽  
Cui-Lin Li ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tnf Α ◽  
Gsk 3Β

Tanshinone IIA Inhibits Epithelial-to-mesenchymal Transition Through Regulating β-arrestin1 Mediated β-catenin Signaling Pathway in Colorectal Cancer

2020 ◽  
Author(s):  
Qing Song ◽  
Liu Yang ◽  
Zhifen Han ◽  
Xinnan Wu ◽  
Ruixiao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Western Blot ◽  
Signaling Pathway ◽  
Lung Metastasis ◽  
Nude Mice ◽  
Epithelial To Mesenchymal Transition ◽  
Tanshinone Iia ◽  
Mesenchymal Transition

Abstract Background: Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the detailed mechanisms of Tan IIA against CRC metastasis are not well explored. Epithelial-to-mesenchymal transition (EMT) exerts an important regulatory role in CRC metastasis, and our previous mechanism studies demonstrated that β-arrestin1 could regulate CRC EMT partly through β-catenin signaling pathway. Therefore, in this work we investigated whether Tan IIA could regulate CRC EMT through β-arrestin1-mediated β-catenin signaling pathway in vivo and in vitro.Methods: The nude mice tail vein metastasis model was established to observe the effect of Tan IIA on CRC lung metastasis in vivo. The lung metastasis was evaluated by living animal imaging and hemaoxylin-eosin staining. The migratory ability of CRC cells in vitro were measured by transwell and wound healing assays. The protein expression and cellular localization of β-arrestin1 and β-catenin were characterized by immunofluorescence staining and western blot. The β-catenin signaling pathway related proteins and EMT associated proteins in CRC cells were detected by western blot and immunohistochemistry. Results: Our results showed that Tan IIA inhibited the lung metastases of CRC cells in vivo and extended the survival time of nude mice. In vitro, Tan IIA increased the expression of E-cadherin, decreased the secretion of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found the mechanism involving in Tan IIA regulating EMT and metastasis, referring to the suppression of β-arrestin1 expression, reduction of β-catenin nuclear localization, thereby the decreased activity of β-catenin signaling. Conclusion: Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway, and provided support for Tan IIA as anti-metastatic agents in CRC.

scholarly journals Lysine-Specific Demethylase 1 Mediates AKT Activity and Promotes Epithelial-to-Mesenchymal Transition in PIK3CA-Mutant Colorectal Cancer

2019 ◽  
Vol 18 (2) ◽  
pp. 264-277 ◽  
Author(s):  
Samuel A. Miller ◽  
Robert A. Policastro ◽  
Sudha S. Savant ◽  
Shruthi Sriramkumar ◽  
Ning Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Lysine Specific Demethylase

scholarly journals Induction of the Epithelial-to-Mesenchymal Transition of Human Colorectal Cancer by Human TNF-β (Lymphotoxin) and its Reversal by Resveratrol

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 704 ◽  
Author(s):  
Constanze Buhrmann ◽  
Mina Yazdi ◽  
Bastian Popper ◽  
Ajaikumar Kunnumakkara ◽  
Bharat Aggarwal ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Invasion Mechanism ◽  
Tnf Α ◽  
Anti Cancer ◽  
Targeted Agent ◽  
And Migration ◽  
Proliferation And Invasion ◽  
Necrosis Factor

Objective: Tumor necrosis factor-beta (TNF-β), as an inflammatory mediator that has been shown to promote tumorigenesis, induces NF-κB. Natural multi-targeted agent resveratrol in turn shows anti-inflammatory and anti-cancer properties. Epithelial-to-mesenchymal transition (EMT) allows cancer cells to turn into a motile state with invasive capacities and is associated with metastasis and development of cancer stem cells (CSC). However, TNF-β-induced EMT and the anti-invasion mechanism of resveratrol on CRC are not yet completely understood. Methods: We investigated the underlying molecular mechanisms of resveratrol on TNF-β/TNF-βR-induced EMT and migration of CRC cells (HCT116, RKO, SW480) in monolayer or 3D alginate cultures. Results: TNF-β, similar to TNF-α, induced significant cell proliferation, morphological change, from an epithelial to a spindle-like mesenchymal shape with the formation of filopodia and lamellipodia associated with the expression of EMT parameters (elevated vimentin and slug, reduced E-cadherin), increased migration/invasion, and formation of CSC in all CRC cells. Interestingly, these effects were dramatically decreased in the presence of resveratrol or anti-TNF-βR with TNF-β co-treatment, inducing biochemical changes to the mesenchymal-epithelial transition (MET), with a planar cell surface and suppressed formation of CSC cells. This was associated with a significant increase in apoptosis. Furthermore, we found that resveratrol suppressed TNF-β-induced NF-κB and NF-κB-regulated gene biomarkers associated with growth, proliferation, and invasion. Finally, TNF-βR interacts directly with focal adhesion kinase (FAK) and NF-κB. Conclusion: These results suggest that resveratrol down-regulates TNF-β/TNF-βR-induced EMT, at least in part via specific suppression of NF-κΒ and FAK in CRC cells.

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