The enhanced expression of PKM2 is involved in the gastric cancer development via regulating cancer specific metabolism

Summary

Recent studies have indicated that an increased expression of the M2 isoform of pyruvate kinase (PKM2) is involved in glycolysis and in tumor development. However, little is known about the role of PKM2 in gastric cancer (GC). Therefore, we examined the expression and function of PKM2 in human GC. We evaluated PKM1 and PKM2 expression by quantitative RT-PCR in gastric tissues from 10 patients who underwent gastric endoscopic submucosal dissection (ESD), 80 patients who underwent gastrectomy, and 7 healthy volunteers, and analyzed the correlation with clinicopathological variables. To assess the function of PKM2, we generated PKM2-knockdown GC cells, and investigated the phenotypic changes. Furthermore, we examined the induction of PKM2 expression by CagA, a pathogenic factor of Helicobacter pylori, using CagA-inducible GC cells.

PKM2 was predominantly expressed not only in GC lesions but also in the normal gastric regions of GC patients and in the gastric mucosa of healthy volunteers. The PKM2 expression was significantly higher in carcinoma compared to non-cancerous tissue and was associated with venous invasion. PKM2 knockdown in GC cells caused significant decreases in cellular proliferation, migration, anchorage-independent growth, and sphere formation in vitro, and in tumor growth and liver metastasis in vivo. The serine concentration-dependent cell proliferation was also inhibited by PKM2 silencing. Furthermore, we found that the PKM2 expression was upregulated by CagA via the Erk pathway.

These results suggested that the enhanced PKM2 expression plays a pivotal role in the carcinogenesis and development of GC in part by regulating cancer-specific metabolism.

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