<b>Conclusions:</b> SAM68 promotes LUAD cell tumorigenesis and cancer metabolic programming via binding of the 351-443 aa region of SAM68 to the RGG motif of hnRNP A1, driving hnRNP A1-dependent <i>PKM</i> splicing, contributing to increased oncogene PKM2 isoform formation and inhibition of PKM1 isoform formation. The gene discussed is PKM; the disease is cancer.