Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can Yoon-Beom Lee and Jung Ki Min contributed equally to this study.

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Src, a non-receptor tyrosine kinase, was first discovered as a prototype oncogene and has been shown to critical for cancer progression for a variety of tissues. Src activity is regulated by a number of post-translational modifications in response to various stimuli. Phosphorylations of Src Tyr419 (human; 416 in chicken) and Src Tyr530 (human; 527 in chicken) have been known to be critical for activation and inactivation of Src, respectively. Wnt signaling regulates a variety of cellular functions including for development and cell proliferation, and has a role in certain diseases such as cancer. Wnt signaling is carried out through two pathways: β-catenin-dependent canonical and β-catenin-independent non-canonical pathways as Wnt ligands bind to their receptors, Frizzled, LRP5/6, and ROR1/2. In addition, many signaling components including Axin, APC, Damm, Dishevelled, JNK kinase and Rho GTPases contribute to these canonical and non-canonical Wnt pathways. However, the communication between Wnt signaling and Src tyrosine kinase has not been well reviewed as Src regulates Wnt signaling through LRP6 tyrosine phosphorylation. GSK-3β phosphorylated by Wnt also regulates Src activity. As Wnt signaling and Src mutually regulate each other, it is noted that aberrant regulation of these components give rise to various diseases including typically cancer, and as such, merit a closer look.