Peroxiredoxin-6 regulates p38-mediated epithelial–mesenchymal transition in HCT116 colon cancer cells

Abstract Background Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial–mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators. Methods We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays. Results We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells. Conclusion We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.

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Epithelial–mesenchymal transition and metastasis of colon cancer cells induced by the FAK pathway in cancer-associated fibroblasts

Journal of International Medical Research ◽

10.1177/0300060520931242 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052093124

Author(s):

Xuefeng Xuefeng ◽

Ming-Xing Hou ◽

Zhi-Wen Yang ◽

Agudamu Agudamu ◽

Feng Wang ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

3D Culture ◽

Cancer Associated Fibroblasts ◽

Colon Cancer Cells ◽

Mesenchymal Transition ◽

Lovo Cells ◽

Related Proteins

Objective The role and mechanism of tetrathiomolybdate (TM) in cancer-associated fibroblasts (CAFs) in colon cancer using three-dimensional (3D) culture were investigated, and the associations between the focal adhesion kinase (FAK) pathway and epithelial–mesenchymal transition (EMT) in CAFs were explored. Methods A 3D co-culture model of colon cancer LOVO cells with CAFs and normal fibroblasts (NFs) was established using Matrigel as a scaffold material. The differential expression of LOXL2 (lysyl oxidase-like 2) in the supernatant of CAFs and NFs was determined using ELISA, and expression levels of EMT-related proteins and FAK signaling pathway-related proteins were determined using western blot. Results LOXL2 levels secreted by CAFs were higher compared with that secreted by NFs. In the CAF + LOVO group, compared with the LOVO group, E-cadherin expression decreased significantly, while N-cadherin and F-PAK expression increased significantly. TM results were opposite compared with the above results. Conclusions CAFs stimulate EMT in human colon cancer LOVO cells by secreting LOXL2 to activate the FAK signaling pathway, thereby promoting tumor metastasis. TM inhibited the occurrence of EMT in the CAF-induced colon cancer LOVO cell line, thereby reducing the invasion and metastasis of colon cancer cells.

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Ginsenoside Rg3 Suppresses Epithelial-Mesenchymal Transition via Downregulating Notch-Hes1 Signaling in Colon Cancer Cells

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500129 ◽

2020 ◽

pp. 1-19

Author(s):

Xiao Li ◽

Wei Liu ◽

Chong Geng ◽

Tingting Li ◽

Yanni Li ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Colon Cancer Cell ◽

Colon Cancer Cells ◽

Ginsenoside Rg3 ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

E Cadherin

Invasion and metastasis are the major causes leading to the high mortality of colon cancer. Ginsenoside Rg3 (Rg3), as a bioactive ginseng compound, is suggested to possess antimetastasis effects in colon cancer. However, the underlying molecular mechanisms remain unclear. In this study, we reported that Rg3 could effectively inhibit colon cancer cell invasion and metastasis through in vivo and in vitro studies. In addition, Rg3 suppressed the epithelial–mesenchymal transition (EMT) of HCT15 cells and SW48 cells evidenced by detecting EMT related markers E-cadherin, vimentin, and snail expression. Furthermore, inhibition of Notch signaling by LY411,575 or specific Hes1 siRNA obviously repressed colon cancer cell migration and metastasis, and induced increase in E-cadherin and decrease in vimentin and snail. Meanwhile, the expression of NICD and Hes1 was obviously decreased in the presence of Rg3. However, Rg3 failed to suppress EMT in Hes1 overexpressed colon cancer cells. In particular, Rg3 significantly reversed IL-6-induced EMT promotion and blocked IL-6- induced NICD and Hes1 upregulations. Overall, these findings suggested that Rg3 could inhibit colon cancer migration and metastasis via suppressing Notch-Hes1-EMT signaling.

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Upregulation of GNL3 expression promotes colon cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway

Oncology Reports ◽

10.3892/or.2017.5923 ◽

2017 ◽

Vol 38 (4) ◽

pp. 2023-2032 ◽

Cited By ~ 12

Author(s):

Xi Tang ◽

Lang Zha ◽

Hui Li ◽

Gang Liao ◽

Zhen Huang ◽

...

Keyword(s):

Colon Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Colon Cancer Cell ◽

Cancer Cell Proliferation ◽

Mesenchymal Transition

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Yeast-Derived Recombinant Avenanthramides Inhibit Proliferation, Migration and Epithelial Mesenchymal Transition of Colon Cancer Cells

Nutrients ◽

10.3390/nu10091159 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1159 ◽

Cited By ~ 5

Author(s):

Federica Finetti ◽

Andrea Moglia ◽

Irene Schiavo ◽

Sandra Donnini ◽

Giovanni Berta ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Epithelial Mesenchymal Transition ◽

Antioxidant Properties ◽

Colon Cancer Cells ◽

Mesenchymal Transition ◽

Molecular Features ◽

Hydroxyanthranilic Acid ◽

The Impact

Avenanthramides (Avns), polyphenols found exclusively in oats, are emerging as promising therapeutic candidates for the treatment of several human diseases, including colon cancer. By engineering a Saccharomyces cerevisiae strain, we previously produced two novel phenolic compounds, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, YAvnI) and N-(E)-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, YAvnII), which are endowed with a structural similarity to bioactive oat avenanthramides and stronger antioxidant properties. In this study, we evaluated the ability of these yeast-derived recombinant avenanthramides to inhibit major hallmarks of colon cancer cells, including sustained proliferation, migration and epithelial-mesenchymal transition (EMT). Using the human colon adenocarcinoma cell line HT29, we compared the impact of YAvns and natural Avns, including Avn-A and Avn-C, on colon cancer cells by performing MTT, clonogenic, adhesion, migration, and anchorage-independent growth assays, and analyzing the expression of EMT markers. We found that both YAvns and Avns were able to inhibit colon cancer cell growth by increasing the expression of p21, p27 and p53 proteins. However, YAvns resulted more effective than natural compounds in inhibiting cancer cell migration and reverting major molecular features of the EMT process, including the down-regulation of E-cadherin mRNA and protein levels.

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