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1.  A novel function of Junctional Adhesion Molecule-C in mediating melanoma cell metastasis 
Cancer research  2011;71(12):4096-4105.
Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified Junctional Adhesion Molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells, promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C−/− mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis.
doi:10.1158/0008-5472.CAN-10-2794
PMCID: PMC3117056  PMID: 21593193
2.  A possible crosstalk between DNA repair pathways and angiogenesis 
Cell cycle (Georgetown, Tex.)  2009;8(21):3438-3439.
Postnatal neovascularization is triggered by tissue hypoxia and the hypoxia-inducible transcription factor dependent upregulation of vascular growth factors. At the same time hypoxia is associated with replication stress and can induce a cellular DNA repair response including the phosphorylation of histone H2AX. Recent findings point to a role of H2AX in endothelial cell proliferation under hypoxia and thereby in hypoxia-driven neovascularization.
PMCID: PMC2783752  PMID: 19838053
4.  Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin–mediated cell–cell contacts 
The Journal of Experimental Medicine  2006;203(12):2703-2714.
We recently reported that junctional adhesion molecule (JAM)-C plays a role in leukocyte transendothelial migration. Here, the role of JAM-C in vascular permeability was investigated in vitro and in vivo. As opposed to macrovascular endothelial cells that constitutively expressed JAM-C in cell–cell contacts, in quiescent microvascular endothelial cells, JAM-C localized mainly intracellularly, and was recruited to junctions upon short-term stimulation with vascular endothelial growth factor (VEGF) or histamine. Strikingly, disruption of JAM-C function decreased basal permeability and prevented the VEGF- and histamine-induced increases in human dermal microvascular endothelial cell permeability in vitro and skin permeability in mice. Permeability increases are essential in angiogenesis, and JAM-C blockade reduced hyperpermeability and neovascularization in hypoxia-induced retinal angiogenesis in mice. The underlying mechanisms of the JAM-C–mediated increase in endothelial permeability were studied. JAM-C was essential for the regulation of endothelial actomyosin, as revealed by decreased F-actin, reduced myosin light chain phosphorylation, and actin stress fiber formation due to JAM-C knockdown. Moreover, the loss of JAM-C expression resulted in stabilization of VE-cadherin–mediated interendothelial adhesion in a manner dependent on the small GTPase Rap1. Together, through modulation of endothelial contractility and VE-cadherin–mediated adhesion, JAM-C helps to regulate vascular permeability and pathologic angiogenesis.
doi:10.1084/jem.20051730
PMCID: PMC2118160  PMID: 17116731

Results 1-4 (4)