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.
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Demaria et al. (2012) studied this question.