Novel mechanism for invasion and metastasis involving metabolic enzymes in intractable cancer cells

Abstract

Cancer metabolism characterizes the malignant behavior of tumors. Pyruvate kinase M2 (PKM2), a key player in maintaining aerobic glycolysis, stimulates tumor growth by controlling the Warburg effect. It has been shown that PKM2 translocates into the nucleus to regulate the transcriptions of numerous down-stream genes, including PDK1 and LDHA. To investigate the significance of PKM2 in epithelial-mesenchymal transition (EMT), a biological process which promotes the metastasis of cancer cells, we induced EMT in gastrointestinal cancer cells using TGFβ and EGF in vitro. After EMT induction, E-cadherin was down-regulated, whereas Vimentin was up-regulated. PKM2 expression was increased at both the transcriptional and the translational level, and PKM2 translocated into the nucleus. Immunohistochemical staining of PKM2 revealed that PKM2 positivity correlated significantly with lymph node metastasis and distant organ metastasis of gastrointestinal cancer. The present results indicate that nuclear PKM2 plays a crucial role in controlling invasion and metastasis.