Peroxiredoxin 1 Promotes Pancreatic Cancer Cell Invasion by Modulating p38 MAPK Activity

Abstract

ObjectiveThe aim of this study was to investigate the role of peroxiredoxin 1 (Prdx1) in the invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells.MethodsImmunohistochemistry was used to determine overexpression of Prdx1 in human PDAC tissues. Immunoprecipitation and immunocytochemistry were used to determine the interaction and intracellular distribution of Prdx1 and a member of the mitogen-activated protein kinase (MAPK) family protein, p38 MAPK, in PDAC cells. Finally, immunocytochemistry and Matrigel invasion assay were used to examine the effects of Prdx1 and p38 MAPK on the formation of cell protrusions and PDAC cell invasion.ResultsPrdx1 is overexpressed in human PDAC tissues. Peroxiredoxin 1 interacts with active forms of p38 MAPK, and complexes of Prdx1 and phosphorylated p38 MAPK localize at the leading edges of migrating PDAC cells. Suppression of Prdx1 decreases active p38 MAPK localized in cell protrusions and inhibits the invasiveness of PDAC cells. Consequently, suppression of Prdx1 inhibits membrane ruffling and protrusions. The p38 MAPK inhibitor SB203580 also decreases the formation of membrane protrusions and inhibits invasiveness.ConclusionsPrdx1 associates with the formation of membrane protrusions through modulation of the activity of p38 MAPK, which in turn promotes PDAC cell invasion.

Endothelium-Derived 5-Methoxytryptophan Is a Circulating Anti-Inflammatory Molecule That Blocks Systemic Inflammation

“…Prdx 1 was reported to enhance p38 MAPK activity and promoting pancreatic cancer cell invasion by directly binding to activated p-p38 MAPK. 24 We wondered whether 5-MTP inhibits p38 MAPK activation by disrupting the interaction between Prdx 1 and p-p38. To examine this possible mechanism, RAW264.7 cells treated with 5-MTP or vehicle followed by lipopolysaccharide were lysed and the lysates were subjected to immunoprecipitation using a selective Prdx 1 antibody or nonimmune IgG.…”

Peroxiredoxin 1 – an antioxidant enzyme in cancer

“…In addition, PRDX1 associates with the formation of membrane protrusions through modulation of the activity of p38MAPK, which in turn promotes pancreatic cancer cell invasion 113. Although the expression of PRDX1 is weak in cervical cancer 114, PRDX1 knockdown significantly enhances HeLa cell sensitivity to ROS‐generating drugs 115.…”

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

“…Some of such regulatory factors have also been contained in our results. MAPK signaling pathway ( hsa04010 ) has been confirmed to have crosstalk with mTOR signaling pathway as we have mentioned above and has been reported to be quite crucial for the invasion and metastasis of pancreatic cancer [80, 81]. Apart from such two functional signaling pathways, another pathway, which has been widely reported to contribute to endometrial cancer, ERBB signaling pathway ( hsa04012 ), is also in Table 1 [82].…”