Metabolism enzyme controls cancer stemness]

Cancer stem cells are known to influence survival, chemoresistance, relapse and metastasis. Pyruvate kinase M2 (PKM2) maintains aerobic glycolysis in cancer cells and stimulates cell proliferation by controlling Warburg effect. In addition, PKM2 translocates to nucleus and up-regulates PDK1 expression by controlling its transcription. PKM2 confers malignant potential by controlling both metabolism and transcriptional regulation. Tumor invasion is initiated with the change of epithelial-mesenchymal transition (EMT) in cancer cell. After EMT induction, in parallel with E-cadherin down-regulation and vimentin up-regulation, the expression of PKM2 was increased both in transcriptional and translational level and PKM2 translocated into nucleus. TGIF2 was identified which interacted with PKM2 in nucleus in response to EMT induction, which was considered to have a key role in controlling EMT induction. We performed immunohistochemical staining with specific antibody to PKM2 using clinical samples of colorectal cancers. Clinicopathological analysis showed that PKM2 positivity significantly correlated with lymph node metastasis and distant organ metastasis. In conclusion, our data suggested that PKM2 nuclear function had a crucial role in controlling invasion and metastasis.