Pyruvate Kinase M2 Coordinates Metabolism Switch between Glycolysis and Glutaminolysis in Cancer Cells

The Emerging Role of Pyruvate Kinase M2 in Regulating Glutaminolysis via c-Myc

“…In addition to c-Myc, many other cancer-progression associated genes have been reported to be regulated by IRES-mediated translation, such as VEGF, IGF1R, cyclin D1 and XIAP [29][30][31][32][33], Furthermore, IRES-mediated translation of these genes have been found critical for many processes of cancer cells including metastasis and angiogenesis [31,34,35]. Interestingly, dimer PKM2 is found to promote cancer cell metastasis and angiogenesis [36,37]. It is plausible that the dimer PKM2 might be able to regulate these genes through IRES-dependent translation.…”

“…between glycolysis and glutaminolysis in cancer cells" [12], the authors demonstrated that the pyruvate kinase M2 (PKM2), a critical enzyme in glycolysis, helps to switch the glutaminolysis pathway in cancer cells through internal ribosome entry site (IRES)-dependent translation of c-Myc. This study uncovers an important mechanism how cancer cells coordinate glycolysis and glutaminolysis and also sheds light on the novel role of PKM2 as a regulator of glutaminolysis.…”

The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer

“…Hence, glutamine metabolism or glutaminolysis is equally essential in the metabolic reprogramming of CRC cells by supporting ATP production and biosynthesis of proteins, lipids, and nucleic acids. The less glycolytic, dimer form of PKM2 is crucial to coordinate the metabolism change between glycolysis and glutaminolysis in CRC cells ( Li L. et al, 2020 ). PKM2 dimer facilitates glutaminolysis upon EGFR stimulation by promoting IRES-dependent c-MYC translation ( Li L. et al, 2020 ).…”

“…The less glycolytic, dimer form of PKM2 is crucial to coordinate the metabolism change between glycolysis and glutaminolysis in CRC cells ( Li L. et al, 2020 ). PKM2 dimer facilitates glutaminolysis upon EGFR stimulation by promoting IRES-dependent c-MYC translation ( Li L. et al, 2020 ). Previously, c-MYC regulates PKM2 expression by controlling PKM2 pre-mRNA splicing, and subsequently, PKM2 regulates c-MYC gene transcription in a direct feedback mechanism ( David et al, 2010 ; Luo et al, 2011 ; Yang et al, 2012 ).…”

“…Previously, c-MYC regulates PKM2 expression by controlling PKM2 pre-mRNA splicing, and subsequently, PKM2 regulates c-MYC gene transcription in a direct feedback mechanism ( David et al, 2010 ; Luo et al, 2011 ; Yang et al, 2012 ). The recent work by Li et al demonstrates that PKM2 interacts with the c-MYC/IRES complex to regulate c-MYC translation via another IRES-dependent mechanism ( Li L. et al, 2020 ). There are two pathways in c-MYC protein synthesis at the translational level: canonical cap-dependent translation and internal ribosome entry site (IRES)-dependent translation ( Godet et al, 2019 ).…”