The Planar Cell Polarity Pathway Drives Pathogenesis of Chronic Lymphocytic Leukemia by the Regulation of B-Lymphocyte Migration

0392609 - BFÚ 2014 RIV US eng J - Journal Article
Kaucká, M. - Plevová, K. - Pavlová, Š. - Janovská, P. - Mishra, A. - Verner, J. - Procházková, J. - Krejčí, Pavel - Kotásková, J. - Ovesná, P. - Tichý, B. - Brychtová, Y. - Doubek, M. - Kozubík, Alois - Mayer, J. - Pospíšilová, Š. - Bryja, Vítězslav
The Planar Cell Polarity Pathway Drives Pathogenesis of Chronic Lymphocytic Leukemia by the Regulation of B-Lymphocyte Migration.
Cancer Research. Roč. 73, č. 5 (2013), s. 1491-1501. ISSN 0008-5472. E-ISSN 1538-7445
R&D Projects: GA ČR(CZ) GD204/09/H058
Grant - others:GA ČR(CZ) GAP301/11/0747; GA ČR(CZ) GAP305/11/0752; GA MŠk(CZ) LH12004; GA MŠk(CZ) ED1.1.00/02.0068
Program: GA; ED
Institutional support: RVO:68081707
Keywords : KINASE-I-EPSILON * SURVIVAL SIGNALS * INHIBITOR
Subject RIV: BO - Biophysics
Impact factor: 9.284, year: 2013

The planar cell polarity (PCP) pathway is a conserved pathway that regulates cell migration and polarity in various contexts. Here we show that key PCP pathway components such as Vangl2, Celsr1, Prickle1, FZD3, FZD7, Dvl2, Dvl3, and casein kinase 1 (CK1)-epsilon are upregulated in B lymphocytes of patients with chronic lymphocytic leukemia (CLL). Elevated levels of PCP proteins accumulate in advanced stages of the disease. Here, we show that PCP pathway is required for the migration and transendothelial invasion of CLL cells and that patients with high expression of PCP genes, FZD3, FZD7, and PRICKLE1, have a less favorable clinical prognosis. Our findings establish that the PCP pathway acts as an important regulator of CLL cell migration and invasion. PCP proteins represent an important class of molecules regulating pathogenic interaction of CLL cells with their microenvironment. Cancer Res; 73(5); 1491-501. (C) 2012 AACR.
Permanent Link: http://hdl.handle.net/11104/0221421