Fig. 2

A schematic diagram illustrating the regulation of PKM2 on the Warburg effect, cancer metastasis and EMT. a Proposed mechanism of PKM2-regulated the Warburg effect. EGFR engagement facilitates PKM2 nuclear translocation. Nuclear PKM2 serves as a coactivator of β-catenin to activate expression of c-Myc, leading to the up-regulation of GLUT1, LDHA and PTB-dependent PKM2 expression. These glycolytic enzymes promote the Warburg effect. b PKM2 promotes cancer invasion and metastasis. Nuclear PKM2 interacts directly with and phosphorylates PAK2, a serine–threonine kinase with a major role in regulating cell mobility. The phosphorylation stabilizes PAK2 by facilitating HSP90 association to PAK2 and thus prevents ubiquitination and proteasomal degradation of PAK2, which increase the cell invasion ability and promote tumor metastasis. c PKM2 regulates EMT. Nuclear PKM2 dimer binds to TGIF2 and promotes its degradation through ubiquitin-proteasome system. This facilitates the recruitment of HDAC3 to the CDH1 promoter, which subsequently deacetylates histone H3 and inhibits CDH1 transcription. Down-regulation of E-cadherin expression induces EMT and promotes tumor cell invasion and metastasis CDH1, E-cadherin; EMT, epithelial mesenchymal transition; GLUT1: glucose transporter 1; HDAC3: histone deacetylase 3; HSP90: heat shock protein 90; LDHA: lactate dehydrogenase A; PAK2: p21 protein activated kinase 2; PTB: polypyrimidine tract binding protein; TGIF2: TGF-β-induced factor homeobox 2