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Macrophage-Associated PGK1 Phosphorylation Promotes Aerobic Glycolysis and Tumorigenesis.
- Source :
-
Molecular Cell . Jul2018, Vol. 71 Issue 2, p201-201. 1p. - Publication Year :
- 2018
-
Abstract
- Summary Macrophages are a dominant leukocyte population in the tumor microenvironment and actively promote cancer progression. However, the molecular mechanism underlying the role of macrophages remains poorly understood. Here we show that polarized M2 macrophages enhance 3-phosphoinositide-dependent protein kinase 1 (PDPK1)-mediated phosphoglycerate kinase 1 (PGK1) threonine (T) 243 phosphorylation in tumor cells by secreting interleukin-6 (IL-6). This phosphorylation facilitates a PGK1-catalyzed reaction toward glycolysis by altering substrate affinity. Inhibition of PGK1 T243 phosphorylation or PDPK1 in tumor cells or neutralization of macrophage-derived IL-6 abrogates macrophage-promoted glycolysis, proliferation, and tumorigenesis. In addition, PGK1 T243 phosphorylation correlates with PDPK1 activation, IL-6 expression, and macrophage infiltration in human glioblastoma multiforme (GBM). Moreover, PGK1 T243 phosphorylation also correlates with malignance and prognosis of human GBM. Our findings demonstrate a novel mechanism of macrophage-promoted tumor growth by regulating tumor cell metabolism, implicating the therapeutic potential to disrupt the connection between macrophages and tumor cells by inhibiting PGK1 phosphorylation. Graphical Abstract Highlights • Macrophages regulate tumor cell aerobic glycolysis through PGK1 • PGK1 T243 phosphorylation regulates the direction of PGK1-catalyzed reaction • Inhibition of PGK1 T243 phosphorylation abrogates protumoral function of macrophages • PGK1 T243 phosphorylation correlates with grades and prognosis of GBM patients Macrophages are a dominant leukocyte population in the tumor microenvironment and actively promote cancer progression. Zhang et al. demonstrate that resident tissue macrophages secrete IL-6 to regulate the direction of a PGK1-catalyzed reaction by increasing PDPK1-dependent PGK1 phosphorylation in tumor cells, promoting tumor cell glycolysis and tumorigenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 71
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 134573413
- Full Text :
- https://doi.org/10.1016/j.molcel.2018.06.023