title: Angiomotin like-1 is a novel component of the N-cadherin complex affecting endothelial/pericyte interaction in normal and tumor angiogenesis.
abstract: Transmission of mechanical force via cell junctions is an important component that molds cells into shapes consistent with proper organ function. Of particular interest are the cadherin transmembrane proteins, which play an essential role in connecting cell junctions to the intra-cellular cytoskeleton. Understanding how these biomechanical complexes orchestrate intrinsic and extrinsic forces is important for our understanding of the underlying mechanisms driving morphogenesis. We have previously identified the Amot protein family, which are scaffold proteins that integrate polarity, junctional, and cytoskeletal cues to modulate cellular shape in endothelial as well as epithelial cells. In this report, we show that AmotL1 is a novel partner of the N-cadherin protein complex. We studied the role of AmotL1 in normal retinal as well as tumor angiogenesis using inducible endothelial-specific knock-out mice. We show that AmotL1 is essential for normal establishment of vascular networks in the post-natal mouse retina as well as in a transgenic breast cancer model. The observed phenotypes were consistent with a non-autonomous pericyte defect. We show that AmotL1 forms a complex with N-cadherin present on both endothelial cells and pericytes. We propose that AmotL1 is an essential effector of the N-cadherin mediated endothelial/pericyte junctional complex.
authors.affiliation: Department of Oncology and Pathology, Cancer Centrum Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Oncology and Pathology, Cancer Centrum Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, 10126 Turin, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barutello
authors.affiliation: Department of Oncology and Pathology, Cancer Centrum Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
authors.forename: Kungchun
authors.initials: K
authors.lastname: Chiu
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, 10126 Turin, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Arigoni
authors.affiliation: Department of Biosciences, Milan University, Via Celoria 26, Milan 20133, Italy and IFOM, the FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.
authors.forename: Costanza
authors.initials: C
authors.lastname: Giampietro
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, 10126 Turin, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Department of Oncology and Pathology, Cancer Centrum Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Holmgren
mesh_terms: D000091304:Angiopoietin-Like Protein 1; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D007365:Intercellular Junctions; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000502:physiology*; D012160:Retina / Q000502:physiology
chemical_list: C449807:Amotl1 protein, mouse; D000091304:Angiopoietin-Like Protein 1; D015820:Cadherins; C489083:Cdh2 protein, mouse; D008565:Membrane Proteins