Abstract
The generation of an "angiogenic switch" is essential for tumor growth, yet its regulation is poorly understood. In this investigation, we explored the linkage between metastasis and angiogenesis through CXCL12/CXCR4 signaling. We found that CXCR4 regulates the expression and secretion of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 reduced the secretion of vascular endothelial growth factor and interleukin-8 and increased the generation of angiostatin. At metastatic sites, however, high levels of CXCL12 signaling through CXCR4 reduced PGK1 expression, releasing the angiogenic response for metastastic growth. These data suggest that PGK1 is a critical downstream target of the chemokine axis and an important regulator of an "angiogenic switch" that is essential for tumor and metastatic growth.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
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Retracted Publication
MeSH terms
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Angiostatins / biosynthesis
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Cell Line, Tumor
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Chemokine CXCL12
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Chemokines, CXC / metabolism
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Gene Expression Regulation, Neoplastic
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Humans
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Interleukin-8 / biosynthesis
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Interleukin-8 / metabolism
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Male
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Neovascularization, Pathologic / enzymology
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism
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Phosphoglycerate Kinase / biosynthesis*
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Phosphoglycerate Kinase / metabolism
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Prostatic Neoplasms / blood supply*
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Prostatic Neoplasms / enzymology
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism*
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Receptors, CXCR4 / metabolism
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Signal Transduction
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Vascular Endothelial Growth Factor A / biosynthesis
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Vascular Endothelial Growth Factor A / metabolism
Substances
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines, CXC
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Interleukin-8
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Receptors, CXCR4
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Vascular Endothelial Growth Factor A
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Angiostatins
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Phosphoglycerate Kinase