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.

Phosphorylation of PBK at Thr9 by CDK5 correlates with invasion of prolactinomas

“…41 Prx6 regulates EMT signaling by reducing p38 phosphorylation in colon cancer cells. 42 The above results confirmed our conjecture. As the function of PBK has been revealed, a variety of PBK small molecule inhibitors have been reported: HI-PBK-032, OTS514, OTS964, and ADA-07 have a strong inhibitory effect on PBK in a variety of tumors.…”

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway

“…These activated genes enable tumor cells to survive in a hypoxic environment and promote invasion and metastasis of tumor cells by directly activating EMT-related genes [ 30 ]. It has been reported that EMT plays a crucial role in CC cells [ 31 ]. Moreover, the downregulation of E-cadherin and the upregulation of N-cadherin and vimentin are considered to be important factors for tumor cells to obtain EMT pathway [ 32 , 33 ].…”

The double homeobox a pseudogene 8 accelerates cell proliferation, migration, and invasion in colon cancer

“…EMT is strongly associated with tumor invasion and metastasis in numerous cancers, including, colon 28 , gastric 29 , and prostate cancers 30 . It was previously demonstrated that several lncRNAs modulate EMT to regulate tumor metastasis 31 , 32 .…”