2023  1,500
2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 58(2024) N 2 p. 300-310; DOI 10.1134/S0026893324020171 Full Text

A. Wang1*, Y.C. Huang1, X.P. Yang1

REEP3 as a Novel Oncogene Contributes to the Warburg Effect in Pancreatic Cancer Cells by Activating the EGFR/ERK Pathway

1Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Ningbo University, Ningbo, 315000 China

Received - 2023-09-12; Revised - 2023-11-08; Accepted - 2023-11-08

Emerging evidence indicates that the Warburg effect (aerobic glycolysis) is a marker of malignancy in pancreatic cancer (PC). Receptor expression-enhancing protein 3 (REEP3) is dysregulated in various cancers; however, no studies have addressed whether REEP3 is involved in regulating PC malignancy, particularly with respect to the Warburg effect. Herein, we identified a new diagnostic marker of PC, which may be useful for developing drugs to treat PC and providing insight into the molecular pathology of PC. The microarray dataset GSE183795 was retrieved from the Gene Expression Omnibus database and the differentially expressed genes were analyzed. REEP3 expression was examined in PC cell lines and normal pancreatic ductal epithelial cells. Following REEP3 knockdown or overexpression in PC cells, cell invasion, migration, glucose uptake, lactate production, ATP levels, and epidermal growth factor receptor (EGFR)/extracellular regulated kinase (ERK) pathway protein expression were assessed via scratch, Transwell, glucose, and lactate assays and western blot analysis. A database analysis revealed that REEP3 was highly expressed in PC tumor tissues from 179 patients. In addition, patients with high REEP3 tumor expression exhibited poor overall and disease-free survival. Our results suggest that REEP3 is upregulated in multiple PC cell lines. Moreover, cell viability indicators, such as proliferation, invasion, migration, glycolytic activity, and EGFR/ERK pathway protein expression were conspicuously restrained on REEP3 disruption in PC cells. Overall, these findings suggest that REEP3 assists PC cell proliferation, invasion, and migration by facilitating the Warburg effect through the activation of the EGFR/ERK signaling pathway.

pancreatic cancer, REEP3, Warburg effect, EGFR/ERK pathway