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DLC2 modulates angiogenic responses in vascular endothelial cells by regulating cell attachment and migration.

Lin Y, Chen NT, Shih YP, Liao YC, Xue L, Lo SH - Oncogene (2010)

Bottom Line: DLC2 is expressed in several tissues and in endothelial cells (ECs) of blood vessels.Silencing of DLC2 in human ECs has reduced cell attachment, increased migration, and tube formation.These changes are rescued by silencing of RhoA, suggesting that the process is RhoA pathway dependent.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Medicine University of California-Davis, Sacramento, CA 95817, USA.

ABSTRACT
Deleted in liver cancer 1 (DLC1) is a RhoGTPase activation protein-containing tumor suppressor that associates with various types of cancer. Although DLC2 shares a similar domain structure with that of DLC1, the function of DLC2 is not well characterized. Here, we describe the expression and ablation of DLC2 in mice using a reporter-knockout approach. DLC2 is expressed in several tissues and in endothelial cells (ECs) of blood vessels. Although ECs and blood vessels show no histological abnormalities and mice appear overall healthy, DLC2-mutant mice display enhanced angiogenic responses induced by matrigel and by tumor cells. Silencing of DLC2 in human ECs has reduced cell attachment, increased migration, and tube formation. These changes are rescued by silencing of RhoA, suggesting that the process is RhoA pathway dependent. These results indicate that DLC2 is not required for mouse development and normal vessel formation, but may protect mouse from unwanted angiogenesis induced by, for example, tumor cells.

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Related in: MedlinePlus

DLC2 regulates HUVEC attachment, migration, and tube formation in a RhoA dependent matterHUVECs transfected with indicated siRNAs were used for immunoblotting analysis to confirm the knockdown efficiencies (A), cell attachment (B), wound healing migration (C), and in vitro angiogenesis assays (D). Representative images were shown. Each assay was independently performed three times. *p<0.05. P-values were calculated by unpaired Student's t test.
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Figure 5: DLC2 regulates HUVEC attachment, migration, and tube formation in a RhoA dependent matterHUVECs transfected with indicated siRNAs were used for immunoblotting analysis to confirm the knockdown efficiencies (A), cell attachment (B), wound healing migration (C), and in vitro angiogenesis assays (D). Representative images were shown. Each assay was independently performed three times. *p<0.05. P-values were calculated by unpaired Student's t test.

Mentions: To analyze the role of DLC2 in endothelial cells and the molecular mechanism involved, we have applied the siRNA approach. Silencing of DLC2 in HUVECs (human umbilical vein endothelial cells) significantly reduced cell attachment and promoted cell migration (figure 5). In addition, down-regulation of DLC2 also enhanced tube formation of HUVEC on matrigel. These in vitro results are consistent with our in vivo findinsg and support the idea that DLC2 negatively regulates angiogenesis by modulating endothelial cell attachment and migration.


DLC2 modulates angiogenic responses in vascular endothelial cells by regulating cell attachment and migration.

Lin Y, Chen NT, Shih YP, Liao YC, Xue L, Lo SH - Oncogene (2010)

DLC2 regulates HUVEC attachment, migration, and tube formation in a RhoA dependent matterHUVECs transfected with indicated siRNAs were used for immunoblotting analysis to confirm the knockdown efficiencies (A), cell attachment (B), wound healing migration (C), and in vitro angiogenesis assays (D). Representative images were shown. Each assay was independently performed three times. *p<0.05. P-values were calculated by unpaired Student's t test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2874629&req=5

Figure 5: DLC2 regulates HUVEC attachment, migration, and tube formation in a RhoA dependent matterHUVECs transfected with indicated siRNAs were used for immunoblotting analysis to confirm the knockdown efficiencies (A), cell attachment (B), wound healing migration (C), and in vitro angiogenesis assays (D). Representative images were shown. Each assay was independently performed three times. *p<0.05. P-values were calculated by unpaired Student's t test.
Mentions: To analyze the role of DLC2 in endothelial cells and the molecular mechanism involved, we have applied the siRNA approach. Silencing of DLC2 in HUVECs (human umbilical vein endothelial cells) significantly reduced cell attachment and promoted cell migration (figure 5). In addition, down-regulation of DLC2 also enhanced tube formation of HUVEC on matrigel. These in vitro results are consistent with our in vivo findinsg and support the idea that DLC2 negatively regulates angiogenesis by modulating endothelial cell attachment and migration.

Bottom Line: DLC2 is expressed in several tissues and in endothelial cells (ECs) of blood vessels.Silencing of DLC2 in human ECs has reduced cell attachment, increased migration, and tube formation.These changes are rescued by silencing of RhoA, suggesting that the process is RhoA pathway dependent.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Medicine University of California-Davis, Sacramento, CA 95817, USA.

ABSTRACT
Deleted in liver cancer 1 (DLC1) is a RhoGTPase activation protein-containing tumor suppressor that associates with various types of cancer. Although DLC2 shares a similar domain structure with that of DLC1, the function of DLC2 is not well characterized. Here, we describe the expression and ablation of DLC2 in mice using a reporter-knockout approach. DLC2 is expressed in several tissues and in endothelial cells (ECs) of blood vessels. Although ECs and blood vessels show no histological abnormalities and mice appear overall healthy, DLC2-mutant mice display enhanced angiogenic responses induced by matrigel and by tumor cells. Silencing of DLC2 in human ECs has reduced cell attachment, increased migration, and tube formation. These changes are rescued by silencing of RhoA, suggesting that the process is RhoA pathway dependent. These results indicate that DLC2 is not required for mouse development and normal vessel formation, but may protect mouse from unwanted angiogenesis induced by, for example, tumor cells.

Show MeSH
Related in: MedlinePlus