Endogenous AJAP1 associates with the cytoskeleton and attenuates angiogenesis in endothelial cells

Abstract

The adherens junction associated protein 1 (AJAP1, aka shrew-1) is presumably a type-I transmembrane protein localizing and interacting with the E-cadherin-catenin complex. In various tumors, AJAP1 expression is reduced or lost, including hepatocellular and esophageal squamous cell carcinoma, and glial-derived tumors. The aberrant expression of AJAP1 is associated with alterations in cell migration, invasion, increased tumor growth, and tumor vascularization, suggesting AJAP1 as a putative tumor suppressor. We show that AJAP1 attenuates sprouting angiogenesis by reducing endothelial migration and invasion capacities. Further, we show for the first time that endogenous AJAP1 is associated with the microtubule cytoskeleton. This linkage is independent from cell confluency and stable during angiogenic sprouting in vitro. Our work suggests that AJAP1 is a putative negative regulator of angiogenesis, reducing cell migration and invasion by interfering with the microtubule network. Based on our results and those of other authors, we suggest AJAP1 as a novel tumor suppressor and diagnostic marker.

MiR‐552 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells by inhibiting AJAP1 expression

“…Hötte et al found that AJAP1 is associated with the cytoskeleton in endothelial cells. 25 Tanaka et al 26 levels were inversely correlated with the levels of SRC in HCC cell lines and tissues, which verified our hypothesis shown in Figure 7. We also demonstrated effects on the downstream proteins E-cadherin…”

“…Hötte et al. found that AJAP1 is associated with the cytoskeleton in endothelial cells . Tanaka et al pointed out the necessity of exploring the correlation between AJAP1 expression, a tumour‐recurrence predictor and EMT markers.…”

Phenotypic Consequences of SLC25A40-ABCB1 Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer

“…Our RNA-seq analysis revealed the putative tumor suppressor AJAP1 as the most highly expressed gene in fusion-positive lines. AJAP1 is a type-1 transmembrane protein that localizes and interacts with the E-cadherin-catenin complex and is involved in cellular processes such as cell migration and invasion by modulating adherens junctions and remodeling the ECM and cytoskeleton [ 52 ]. For example, in nonpolarized, highly migratory and invasive cells, AJAP1 interacts with the transmembrane glycoprotein CD147, an invasion-promoting protein [ 53 ].…”

Genetic analysis of the molecular regulation of electric fields-guided glia migration

“…The adherens junctions associated protein 1 (AJAP1) is a type-I transmembrane protein that localizes and interacts with the E-cadherin-catenin complex. The endogenous AJAP1 is associated with the microtubule cytoskeleton and can attenuate sprouting angiogenesis by reducing endothelial migration and invasion capacities 47 .…”