Abstract
Background and AimsEGFR activation and PKM2 expression are instrumental in tumorigenesis. EGFR activation regulates PKM2 functions in a subcellular compartment-dependent manner and promotes gene transcription and tumor growth. In addition, PKM2 is upregulated in EGFR-induced pathways in glioma malignancies. However, we found that PKM2 could also regulate the activity of the EGF/EGFR signaling pathway in gastric cancer cells. We aimed to define the biological mechanisms for PKM2 in regulating the cell motility and invasion.MethodsWe employed stable transfection with short hairpin RNA to stably silence the expression of PKM2 in the BGC823, SGC7901 and AGS gastric cancer cell lines. The effects of PKM2 in vitro were determined by assessing cell migration and invasion. Immunohistochemical analysis was used to explore the relationship among PKM2 and other proteins.ResultsOur results indicate that the knockdown of PKM2 decreased the activity of E-cadherin and enhanced the EGF/EGFR signaling pathway in the gastric cell lines BGC823 and SGC7901 that were positive for E-cadherin expression. However, in the undifferentiated gastric carcinoma cell line AGS, which lacks E-cadherin expression, PKM2 promoted cell migration and invasion. Immunohistochemical analyses showed that the levels of E-cadherin expression, ERK1/2 phosphorylation, and cytoplasmic PKM2 expression were correlated with each other.Conclusion:PKM2 may play different roles in differently differentiated gastric cancer cell types, and this finding would be consistent with the previous clinical research. The results of our study reveal an important link between PKM2 and E-cadherin during EGFR-stimulated gastric cancer cell motility and invasion.
Highlights
Pyruvate kinase (PK) mediates the final rate-limiting step of glycolysis by catalyzing the dephosphorylation of phosphoenolpyruvate (PEP) to pyruvate to yield one molecule of ATP
Our results indicate that the knockdown of PKM2 decreased the activity of E-cadherin and enhanced the epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling pathway in the gastric cell lines BGC823 and SGC7901 that were positive for E-cadherin expression
Immunohistochemical analyses showed that the levels of E-cadherin expression, ERK1/2 phosphorylation, and cytoplasmic PKM2 expression were correlated with each other
Summary
Pyruvate kinase (PK) mediates the final rate-limiting step of glycolysis by catalyzing the dephosphorylation of phosphoenolpyruvate (PEP) to pyruvate to yield one molecule of ATP. A recent study confirmed that the PKM2 induced by epidermal growth factor (EGF) translocates into the nucleus of glioblastoma cells, interacts with b-catenin and leads to cyclinD1 expression, which promotes cell proliferation and tumorigenesis [6]. These findings reveal a novel role for PKM2 as a transcriptional coactivator. EGFR activation regulates PKM2 functions in a subcellular compartment-dependent manner and promotes gene transcription and tumor growth. We found that PKM2 could regulate the activity of the EGF/EGFR signaling pathway in gastric cancer cells. We aimed to define the biological mechanisms for PKM2 in regulating the cell motility and invasion
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