Which of the pyruvate kinase isoforms are involved in glycolysis changes in cancer cells?

Because the low activity PKM2 dimer is the major isoform that triggers glycolysis in the cytoplasm and gene transcription in the nucleus in cancer cells, PKM2 activators which can promote the formation of tetrameric PKM2 may switch glycolysis to mitochondria pathway and reduce nuclear entry to attenuate gene …

How does pyruvate kinase work?

Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. There are four mammalian pyruvate kinase isoforms with unique tissue expression patterns and regulatory properties.

How does PKM2 play a role in cancer cells?

PKM2 provides an in vivo growth advantage in cancer cells by its preferential expression and allosteric enzymatic activity without accumulation of ROS ( 24 ). The switching between the high-activity and low-activity states of PKM2 is subjected to allosteric regulation.

Where is PKM2 found in the human body?

PKM2 is expressed in some differentiated tissues, such as lung, fat tissue, retina, and pancreatic islets, as well as in all cells with a high rate of nucleic acid synthesis, such as normal proliferating cells, embryonic cells, and especially tumor cells.

How does PKM2 activate glycolytic inhibitor 2DG?

PKM2 pharmacological activation was shown to potentiate the anticancer effects of the glycolytic inhibitor 2-deoxyglucose (2DG) in cancer cells from different tissue origin [ 21 ]. Besides, PKM2 deletion was shown to increase the formation of tumors in a mouse model of breast cancer [ 22 ].

What kind of mutations are found in PKM2?

Two missense mutations, H391Y and K422R, of PKM2 were found in cells from Bloom syndrome patients prone to developing cancer. Results show that, despite the presence of mutations in the inter-subunit contact domain, the K422R and H391Y mutant proteins maintained their homotetrameric structure, similar to the wild-type protein]