PKM2, STAT3 and HIF-1α: The Warburg's vicious circle.
The M2 isoform of pyruvate kinase, highly expressed in tumor cells, is known to engage a feed forward loop with the glycolysis master transcription factor HIF-1α. Gao and co-authors recently showed that dimeric PKM2 localizes to the nucleus in highly proliferating cancer cells, where it regulates in vivo growth by acting as a protein kinase and directly activating STAT3. STAT3 is therefore a novel player of the PKM2/HIF-1α feedback loop, since HIF-induced PKM2 activates STAT3 that in turn induces HIF-1α expression. These findings have profound implications for understanding the complex connections between gene regulation, metabolism, survival and proliferation in cancer.
Buck Institute for Research on Aging; Novato, CA USA.
Marco
M
Demaria
Valeria
V
Poli
PKM2; STAT3; Warburg; cancer; cell proliferation; glycolysis; growth factors; malignant transformation; pyruvate kinase isoforms