title: Protein interacting with C kinase 1 suppresses invasion and anchorage-independent growth of astrocytic tumor cells.
abstract: Astrocytic tumors are the most common form of primary brain tumor. Astrocytic tumor cells infiltrate the surrounding CNS tissue, allowing them to evade removal upon surgical resection of the primary tumor. Dynamic changes to the actin cytoskeleton are crucial to cancer cell invasion, but the specific mechanisms that underlie the particularly invasive phenotype of astrocytic tumor cells are unclear. Protein interacting with C kinase 1 (PICK1) is a PDZ and BAR domain-containing protein that inhibits actin-related protein 2/3 (Arp2/3)-dependent actin polymerization and is involved in regulating the trafficking of a number of cell-surface receptors. Here we report that, in contrast to other cancers, PICK1 expression is down-regulated in grade IV astrocytic tumor cell lines and also in clinical cases of the disease in which grade IV tumors have progressed from lower-grade tumors. Exogenous expression of PICK1 in the grade IV astrocytic cell line U251 reduces their capacity for anchorage-independent growth, two-dimensional migration, and invasion through a three-dimensional matrix, strongly suggesting that low PICK1 expression plays an important role in astrocytic tumorigenesis. We propose that PICK1 negatively regulates neoplastic infiltration of astrocytic tumors and that manipulation of PICK1 is an attractive possibility for therapeutic intervention.
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Louisa M R
authors.initials: LM
authors.lastname: Cockbill
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Kai
authors.initials: K
authors.lastname: Murk
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, United Kingdom.
authors.forename: Seth
authors.initials: S
authors.lastname: Love
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom jon.hanley@bristol.ac.uk.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Hanley
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics*; D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D002352:Carrier Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human