Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/14398
Title: Stable knockdown of polycystin-1 confers integrin-alpha2beta1-mediated anoikis resistance.
Authors: Battini, L
Fedorova, E
Macip, S
Li, X
Wilson, PD
Gusella, GL
First Published: Nov-2006
Citation: J AM SOC NEPHROL, 2006, 17 (11), pp. 3049-3058
Abstract: The mechanisms of action of polycystin-1 (PC1) have been difficult to dissect because of its interaction with multiple factors, the heterogeneity of the genetic mutations, and the complexity of the experimental animal models. Here, stable knockdown of PC1 in MDCK epithelial cells was achieved by lentiviral-mediated delivery of a specific small interfering RNA for PKD1. The reduction of PC1 expression prevented tubulogenesis in three-dimensional collagen type I culture in response to hepatocyte growth factor and induced formation of cysts. PC1 knockdown created a condition of haploinsufficiency that led to hyperproliferation, increased adhesion to collagen type I, and increased apoptosis. It was shown that the suppression of PC1 was associated with the increased expression of integrin-alpha2beta1 and reduced apoptosis in cells grown on collagen type I. The engagement of integrin-alpha2beta1 seemed to be essential for the survival because PC1 knockdown cells were significantly less susceptible to anoikis by a mechanism that was reversible by anti-integrin-alpha2beta1 blocking antibodies. Overall, these data link integrin-alpha2beta1 to some of the biologic functions that are ascribed to PC1 and establish the potential of this approach for the direct study of PC1 functions in a genetically defined background. Furthermore, these findings indicate that reduction of PC1 expression levels, rather than the loss of heterozygosity, may be sufficient to induce cystogenesis.
DOI Link: 10.1681/ASN.2006030234
ISSN: 1046-6673
Links: http://hdl.handle.net/2381/14398
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

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