A study published in *Nature* (2010) reveals that the oncogenic transcription factor c-Myc regulates the expression of three heterogeneous nuclear ribonucleoprotein (hnRNP) proteins—polypyrimidine tract binding protein (PTB), hnRNPA1, and hnRNPA2—which in turn control the alternative splicing of the pyruvate kinase (PKM) mRNA. This splicing determines the expression of PKM isoforms, PKM1 and PKM2. PKM2 promotes aerobic glycolysis, a metabolic pathway favored by cancer cells, while PKM1 is involved in oxidative phosphorylation. The study shows that c-Myc upregulates the expression of PTB, hnRNPA1, and hnRNPA2, leading to increased PKM2 expression and promoting tumor growth. The hnRNP proteins bind to sequences flanking exon 9 of the PKM pre-mRNA, repressing its inclusion and promoting the inclusion of exon 10. This results in the production of PKM2, which is essential for aerobic glycolysis in cancer cells. The study also demonstrates that in human gliomas, c-Myc, PTB, hnRNPA1, and hnRNPA2 are overexpressed, correlating with high PKM2 levels. Knockdown of these proteins in cell lines leads to increased PKM1 expression and reduced PKM2, indicating their critical role in maintaining PKM2 expression. The study further shows that c-Myc directly regulates the transcription of PTB, hnRNPA1, and hnRNPA2. In NIH-3T3 cells, c-Myc knockdown reduces the levels of these proteins and increases the PKM1/PKM2 ratio. The findings suggest that the regulation of PKM splicing by c-Myc and these hnRNP proteins is essential for tumor cell proliferation. The study highlights the importance of alternative splicing in cancer metabolism and identifies a key regulatory pathway involving c-Myc and hnRNP proteins that controls PKM isoform expression. This pathway is critical for tumor growth and may represent a therapeutic target in cancer treatment.A study published in *Nature* (2010) reveals that the oncogenic transcription factor c-Myc regulates the expression of three heterogeneous nuclear ribonucleoprotein (hnRNP) proteins—polypyrimidine tract binding protein (PTB), hnRNPA1, and hnRNPA2—which in turn control the alternative splicing of the pyruvate kinase (PKM) mRNA. This splicing determines the expression of PKM isoforms, PKM1 and PKM2. PKM2 promotes aerobic glycolysis, a metabolic pathway favored by cancer cells, while PKM1 is involved in oxidative phosphorylation. The study shows that c-Myc upregulates the expression of PTB, hnRNPA1, and hnRNPA2, leading to increased PKM2 expression and promoting tumor growth. The hnRNP proteins bind to sequences flanking exon 9 of the PKM pre-mRNA, repressing its inclusion and promoting the inclusion of exon 10. This results in the production of PKM2, which is essential for aerobic glycolysis in cancer cells. The study also demonstrates that in human gliomas, c-Myc, PTB, hnRNPA1, and hnRNPA2 are overexpressed, correlating with high PKM2 levels. Knockdown of these proteins in cell lines leads to increased PKM1 expression and reduced PKM2, indicating their critical role in maintaining PKM2 expression. The study further shows that c-Myc directly regulates the transcription of PTB, hnRNPA1, and hnRNPA2. In NIH-3T3 cells, c-Myc knockdown reduces the levels of these proteins and increases the PKM1/PKM2 ratio. The findings suggest that the regulation of PKM splicing by c-Myc and these hnRNP proteins is essential for tumor cell proliferation. The study highlights the importance of alternative splicing in cancer metabolism and identifies a key regulatory pathway involving c-Myc and hnRNP proteins that controls PKM isoform expression. This pathway is critical for tumor growth and may represent a therapeutic target in cancer treatment.