Astroprincin (FAM171A1, C10orf38): A regulator of human cell shape and invasive growth

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Rasila , T , Saavalainen , O , Attalla , H , Lankila , P , Haglund , C , Hölttä , E & Andersson , L C 2019 , ' Astroprincin (FAM171A1, C10orf38): A regulator of human cell shape and invasive growth ' , The American Journal of Pathology , vol. 189 , no. 1 , pp. 177-189 . https://doi.org/10.1016/j.ajpath.2018.09.006

Title: Astroprincin (FAM171A1, C10orf38): A regulator of human cell shape and invasive growth
Author: Rasila, Tiina; Saavalainen, Olga; Attalla, Hesham; Lankila, Petri; Haglund, Caj; Hölttä, Erkki; Andersson, Leif C.
Contributor: University of Helsinki, Department of Pathology
University of Helsinki, Department of Pathology
University of Helsinki, HUSLAB
University of Helsinki, Medicum
University of Helsinki, Medicum
Date: 2019-01
Language: eng
Number of pages: 13
Belongs to series: The American Journal of Pathology
ISSN: 0002-9440
URI: http://hdl.handle.net/10138/294751
Abstract: Our group originally found and cloned cDNA for a 98-kDa type 1 transmembrane glycoprotein of unknown function. Because of its abundant expression in astrocytes, it was called the protein astroprincin (APCN). Two thirds of the evolutionarily conserved protein is intracytoplasmic, whereas the extracellular domain carries two N-glycosidic side chains. APCN is physiologically expressed in placental trophoblasts, skeletal and hearth muscle, and kidney and pancreas. Overexpression of APCN (cDNA) in various cell lines induced sprouting of slender projections, whereas knockdown of APCN expression by siRNA caused disappearance of actin stress fibers. Immunohistochemical staining of human cancers for endogenous APCN showed elevated expression in invasive tumor cells compared with intratumoral cells. Human melanoma cells (SK-MEL-28) transfected with APCN cDNA acquired the ability of invasive growth in semisolid medium (Matrigel) not seen with control cells. A conserved carboxyterminal stretch of 21 amino acids was found to be essential for APCN to induce cell sprouting and invasive growth. Yeast two-hybrid screening revealed several interactive partners, of which ornithine decarboxylase antizyme-1, NEEP21 (NSG1), and ADAM10 were validated by coimmunoprecipitation. This is the first functional description of APCN. These data show that APCN regulates the dynamics of the actin cytoskeletal and, thereby, the cell shape and invasive growth potential of tumor cells.
Subject: 3122 Cancers
1182 Biochemistry, cell and molecular biology
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