Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells

S. H. Hsieh, N. W. Ying, M. H. Wu, W. F. Chiang, C. L. Hsu, Dung-Yau Wang, Y. T. Jin, Tse-Ming Hong, Yuh-Ling Chen

研究成果: Article

135 引文 (Scopus)

摘要

Galectin-1 (Gal-1), a homodimeric prototype of the galectins with a single carbohydrate-recognition domain, was recently identified as being overexpressed in tumor-associated capillary endothelial cells. The role of Gal-1 in endothelial cellular functions and the mechanism of action of Gal-1 remain unknown. Neuropilin-1 (NRP1) is a neuronal receptor that mediates repulsive growth cone guidance, and NRP1 functions in endothelial cells as a coreceptor (with vascular endothelial growth factor receptors (VEGFRs)) for VEGF 165. In this study, we found that Gal-1 was overexpressed in the tumor-associated endothelial cells of oral squamous cell carcinomas (P<0.001). Gal-1 increased the proliferation and adhesion of endothelial cells, and enhanced cell migration in combination with VEGF165. Surprisingly, Gal-1 selectively bound NRP1 via the carbohydrate-recognition domain, but did not bind VEGFR-1, VEGFR-2 or VEGFR-3. The Gal-1-NRP1 interaction mediated the migration and adhesion of endothelial cells. The binding of Gal-1 to NRP1 enhanced VEGFR-2 phosphorylation and stimulated the activation of the mitogen activated protein (MAP) kinases SAPK1/JNK (stress activated protein kinase-1/c-Jun NH2-terminal kinase). These findings show, for the first time, that Gal-1 can directly bind to NRP1 on endothelial cells, and can promote the NRP1/VEGFR-2-mediated signaling pathway as well as NRP1-mediated biological activities.

原文English
頁(從 - 到)3746-3753
頁數8
期刊Oncogene
27
發行號26
DOIs
出版狀態Published - 2008 六月 12

指紋

Neuropilin-1
Galectin 1
Vascular Endothelial Growth Factor Receptor-2
Endothelial Cells
Ligands
Carbohydrates
Vascular Endothelial Growth Factor Receptor-3
MAP Kinase Kinase 4
Galectins
Vascular Endothelial Growth Factor Receptor-1
Growth Cones
Vascular Endothelial Growth Factor Receptor
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Cell Movement
Squamous Cell Carcinoma
Neoplasms
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

引用此文

Hsieh, S. H. ; Ying, N. W. ; Wu, M. H. ; Chiang, W. F. ; Hsu, C. L. ; Wang, Dung-Yau ; Jin, Y. T. ; Hong, Tse-Ming ; Chen, Yuh-Ling. / Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. 於: Oncogene. 2008 ; 卷 27, 編號 26. 頁 3746-3753.
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abstract = "Galectin-1 (Gal-1), a homodimeric prototype of the galectins with a single carbohydrate-recognition domain, was recently identified as being overexpressed in tumor-associated capillary endothelial cells. The role of Gal-1 in endothelial cellular functions and the mechanism of action of Gal-1 remain unknown. Neuropilin-1 (NRP1) is a neuronal receptor that mediates repulsive growth cone guidance, and NRP1 functions in endothelial cells as a coreceptor (with vascular endothelial growth factor receptors (VEGFRs)) for VEGF 165. In this study, we found that Gal-1 was overexpressed in the tumor-associated endothelial cells of oral squamous cell carcinomas (P<0.001). Gal-1 increased the proliferation and adhesion of endothelial cells, and enhanced cell migration in combination with VEGF165. Surprisingly, Gal-1 selectively bound NRP1 via the carbohydrate-recognition domain, but did not bind VEGFR-1, VEGFR-2 or VEGFR-3. The Gal-1-NRP1 interaction mediated the migration and adhesion of endothelial cells. The binding of Gal-1 to NRP1 enhanced VEGFR-2 phosphorylation and stimulated the activation of the mitogen activated protein (MAP) kinases SAPK1/JNK (stress activated protein kinase-1/c-Jun NH2-terminal kinase). These findings show, for the first time, that Gal-1 can directly bind to NRP1 on endothelial cells, and can promote the NRP1/VEGFR-2-mediated signaling pathway as well as NRP1-mediated biological activities.",
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Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. / Hsieh, S. H.; Ying, N. W.; Wu, M. H.; Chiang, W. F.; Hsu, C. L.; Wang, Dung-Yau; Jin, Y. T.; Hong, Tse-Ming; Chen, Yuh-Ling.

於: Oncogene, 卷 27, 編號 26, 12.06.2008, p. 3746-3753.

研究成果: Article

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AU - Hsieh, S. H.

AU - Ying, N. W.

AU - Wu, M. H.

AU - Chiang, W. F.

AU - Hsu, C. L.

AU - Wang, Dung-Yau

AU - Jin, Y. T.

AU - Hong, Tse-Ming

AU - Chen, Yuh-Ling

PY - 2008/6/12

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N2 - Galectin-1 (Gal-1), a homodimeric prototype of the galectins with a single carbohydrate-recognition domain, was recently identified as being overexpressed in tumor-associated capillary endothelial cells. The role of Gal-1 in endothelial cellular functions and the mechanism of action of Gal-1 remain unknown. Neuropilin-1 (NRP1) is a neuronal receptor that mediates repulsive growth cone guidance, and NRP1 functions in endothelial cells as a coreceptor (with vascular endothelial growth factor receptors (VEGFRs)) for VEGF 165. In this study, we found that Gal-1 was overexpressed in the tumor-associated endothelial cells of oral squamous cell carcinomas (P<0.001). Gal-1 increased the proliferation and adhesion of endothelial cells, and enhanced cell migration in combination with VEGF165. Surprisingly, Gal-1 selectively bound NRP1 via the carbohydrate-recognition domain, but did not bind VEGFR-1, VEGFR-2 or VEGFR-3. The Gal-1-NRP1 interaction mediated the migration and adhesion of endothelial cells. The binding of Gal-1 to NRP1 enhanced VEGFR-2 phosphorylation and stimulated the activation of the mitogen activated protein (MAP) kinases SAPK1/JNK (stress activated protein kinase-1/c-Jun NH2-terminal kinase). These findings show, for the first time, that Gal-1 can directly bind to NRP1 on endothelial cells, and can promote the NRP1/VEGFR-2-mediated signaling pathway as well as NRP1-mediated biological activities.

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