Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-12

AUTHORS

Weiwei Yang, Yan Xia, Haitao Ji, Yanhua Zheng, Ji Liang, Wenhua Huang, Xiang Gao, Kenneth Aldape, Zhimin Lu

ABSTRACT

The 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 effect, its non-metabolic functions remain elusive. Here we demonstrate, in human cancer cells, that epidermal growth factor receptor (EGFR) activation induces translocation of PKM2, but not PKM1, into the nucleus, where K433 of PKM2 binds to c-Src-phosphorylated Y333 of β-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 β-catenin transactivation is instrumental in EGFR-promoted tumour cell proliferation and brain tumour development. In addition, positive correlations have been identified between c-Src activity, β-catenin Y333 phosphorylation and PKM2 nuclear accumulation in human glioblastoma specimens. Furthermore, levels of β-catenin phosphorylation and nuclear PKM2 have been correlated with grades of glioma malignancy and prognosis. These findings reveal that EGF induces β-catenin transactivation via a mechanism distinct from that induced by Wnt/Wingless and highlight the essential non-metabolic functions of PKM2 in EGFR-promoted β-catenin transactivation, cell proliferation and tumorigenesis. More... »

PAGES

118

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature10598

DOI

http://dx.doi.org/10.1038/nature10598

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030215402

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22056988


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