Endogenous AJAP1 associates with the cytoskeleton and attenuates angiogenesis in endothelial cells
Katharina Hötte,
Isabell Smyrek,
Anna Starzinski-Powitz,
Ernst H. K. Stelzer
Affiliations
Katharina Hötte
Physical Biology/Physikalische Biologie (IZN, FB 15), Buchmann Institute for Molecular Life Sciences (BMLS), Cluster of Excellence Frankfurt – Macromolecular Complexes (CEF – MC), Goethe Universität – Frankfurt am Main (Campus Riedberg), Max-von-Laue-Straße 15, Frankfurt am Main D-60438, Germany
Isabell Smyrek
Physical Biology/Physikalische Biologie (IZN, FB 15), Buchmann Institute for Molecular Life Sciences (BMLS), Cluster of Excellence Frankfurt – Macromolecular Complexes (CEF – MC), Goethe Universität – Frankfurt am Main (Campus Riedberg), Max-von-Laue-Straße 15, Frankfurt am Main D-60438, Germany
Anna Starzinski-Powitz
Institute of Cell Biology and Neuroscience, Department of Molecular Cell Biology and Human Genetics, Goethe Universität – Frankfurt am Main (Campus Riedberg), Max-von-Laue-Straße 13, Frankfurt am Main D-60438, Germany
Ernst H. K. Stelzer
Physical Biology/Physikalische Biologie (IZN, FB 15), Buchmann Institute for Molecular Life Sciences (BMLS), Cluster of Excellence Frankfurt – Macromolecular Complexes (CEF – MC), Goethe Universität – Frankfurt am Main (Campus Riedberg), Max-von-Laue-Straße 15, Frankfurt am Main D-60438, Germany
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.
