detailed methodology can be found in the supplementary information . in short , luciferase reporter gene assay , immunoprecipitation and immunoblotting analysis , purification of recombinant proteins , in vitro kinase assays , and cell migration assay were performed , as previously described .
 summarythe embryonic pyruvate kinase m2 ( pkm2 ) isoform is highly expressed in human cancer . 
 in contrast to the established role of pkm2 in aerobic glycolysis or the warburg effect1,2,3 , its nonmetabolic functions remain elusive . here we demonstrate that egfr activation induces translocation of pkm2 , but not pkm1 , into the nucleus , where k433 of pkm2 binds to c - src - phosphorylated y333 of -catenin . 
 this interaction is required for both proteins to be recruited to the ccnd1 promoter , leading to hdac3 removal from the promoter , histone h3 acetylation , and cyclin d1 expression . 
 pkm2-dependent -catenin transactivation is instrumental in egfr - promoted tumor cell proliferation and brain tumor development . 
 in addition , positive correlations have been identified among c - src activity , -catenin y333 phosphorylation , and pkm2 nuclear accumulation in human glioblastoma specimens . 
 furthermore , levels of -catenin phosphorylation and nuclear pkm2 have been correlated with grades of glioma malignancy and prognosis . 
 these findings reveal that egf induces -catenin transactivation via a mechanism distinct from that induced by wnt / wingless4 and highlight the essential nonmetabolic functions of pkm2 in egfr - promoted -catenin transactivation , cell proliferation , and tumorigenesis . 
METHODS SUMMARY
Supplementary Material