title: A glycolytic mechanism regulating an angiogenic switch in prostate cancer.
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.
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, MI 48109, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Jincheng
authors.initials: J
authors.lastname: Wang
authors.forename: Jinlu
authors.initials: J
authors.lastname: Dai
authors.forename: Younghun
authors.initials: Y
authors.lastname: Jung
authors.forename: Chuen-Long
authors.initials: CL
authors.lastname: Wei
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Havens
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Hogg
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Nor
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
mesh_terms: D043168:Angiostatins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000096:biosynthesis* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016209:Interleukin-8; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D043168:Angiostatins; D010735:Phosphoglycerate Kinase