DLC2 modulates angiogenic responses in vascular endothelial cells by regulating cell attachment and migration.
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.
Lin
Y
Y
Department of Biochemistry and Molecular Medicine University of California-Davis, Sacramento, CA 95817, USA.
Chen
N-T
NT
Shih
Y-P
YP
Liao
Y-C
YC
Xue
L
L
Lo
S H
SH
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D020690:GTPase-Activating Proteins; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D034741:RNA, Small Interfering / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
D020690:GTPase-Activating Proteins; D034741:RNA, Small Interfering; C473607:STARD13 protein, human; C473606:Stard13 protein, mouse; D025521:Tumor Suppressor Proteins; D020742:rhoA GTP-Binding Protein