The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation
Open accessAbstract
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.
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Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
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Otto Warburg's contributions to current concepts of cancer metabolism
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The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
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Pyruvate kinase M2 is a phosphotyrosine-binding protein
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Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells
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Cited by
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
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The many faces and functions of β‐catenin
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“Other nuclear functions of dimeric PKM2 includes the ability to act as a protein kinase, activating transcription of mek5 through phosphorylation of STAT3(Gao et al., 2012) as well as promoting β-catenin translocation, leading to expression of cyclinD1 and c-myc(Yang et al., 2011).”
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335
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Metadata
- Authors
- Yang, W., Xia, Y., Ji, H., Zheng, Y., Liang, J., Huang, W., Gao, X., Aldape, K., & Lu, Z.
- Venue
- Nature
- Published
- 2011-12-01
- Volume
- 480
- Issue
- 7375
- Pages
- 118-122
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2106204137
- Cited by
- 1,028
- References
- 7
- FWCI
- 21.98
- Type
- journal article
- Language
- en
- Open access
- green
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- Yang, W., Xia, Y., Ji, H., Zheng, Y., Liang, J., Huang, W., Gao, X., Aldape, K., & Lu, Z. (2011). Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature. https://doi.org/10.1038/nature10598
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