Chloride intracellular channel 1 functions in endothelial cell growth and migration

Abstract

BackgroundLittle is known about the role of CLIC1 in endothelium. These studies investigate CLIC1 as a regulator of angiogenesis by in vitro techniques that mimic individual steps in the angiogenic process.MethodsUsing shRNA against clic1, we determined the role of CLIC1 in primary human endothelial cell behavior.ResultsHere, we report that reduced CLIC1 expression caused a reduction in endothelial migration, cell growth, branching morphogenesis, capillary-like network formation, and capillary-like sprouting. FACS analysis showed that CLIC1 plays a role in regulating the cell surface expression of various integrins that function in angiogenesis including β1 and α3 subunits, as well as αVβ3 and αVβ5.ConclusionsTogether, these results indicate that CLIC1 is required for multiple steps of in vitro angiogenesis and plays a role in regulating integrin cell surface expression.

Chloride Intracellular Channel 1 Regulates Prostate Cancer Cell Proliferation and Migration Through the MAPK/ERK Pathway

“…25 An elevated CLIC1 expression was strongly correlated with lymph node metastasis, perineural and lymphatic invasion, pathological staging, and poor survival. 26 However, the biological function and molecular mechanisms of CLIC1 in prostate cancer remain unclear.…”

Identification of Vascular Breast Tumor Markers by Laser Capture Microdissection and Label-Free LC−MS

“…In other cancers, the expression of Clic-1 has been shown to correlate with metastatic potential. 47,50 Furthermore, the genetic knockout of another Clic family member, Clic-4, leads to angiogenic defects in mice 51 and Clic-1 regulates endothelial cell growth and migration in culture, 52 suggesting the expression of Clic-1 in tumor vasculature seen in our proteomic and IHC studies may play a role in regulating tumor angiogenesis.…”

Tips, Stalks, Tubes: Notch-Mediated Cell Fate Determination and Mechanisms of Tubulogenesis during Angiogenesis

“…Although not necessarily an effector of tubulogenesis, CLIC1 is also receiving attention as being a potential regulator of angiogenesis. In vitro CLIC1 plays a role in endothelial cell migration, proliferation, and branching morphogenesis; however, no notable effect on lumen formation results from knocking down CLIC1 levels (Tung and Kitajewski 2010). CLIC1 may also affect apical membrane recycling as it is localized to the apical domain in several columnar epithelia (Ulmasov et al 2007).…”

“…They exist as both soluble cytoplasmic proteins and membrane bound channel proteins with a putative transmembrane domain near the amino terminus, making them unique as mammalian ion channels (Redhead et al 1997;Berry and Hobert 2006). Of the six known mammalian CLICs, only CLIC1 and CLIC4 are expressed highly in endothelial cells Money et al 2007;Suh et al 2007;Ulmasov et al 2007;Tung et al 2009;Tung and Kitajewski 2010;Wegner et al 2010). In addition, CLIC5 levels are found to be low in placental endothelial cells (Money et al 2007) and high in glomerular endothelial cells (Wegner et al 2010).…”