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

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Authors

KAUCKÁ Markéta PLEVOVÁ Karla PAVLOVÁ Šárka JANOVSKÁ Pavlína SHAIK Archana VERNER Jan PROCHÁZKOVÁ Jiřina KREJČÍ Pavel KOTAŠKOVÁ Jana OVESNÁ Petra TICHÝ Boris BRYCHTOVÁ Yvona DOUBEK Michael KOZUBÍK Alois MAYER Jiří POSPÍŠILOVÁ Šárka BRYJA Vítězslav

Year of publication 2013
Type Article in Periodical
Magazine / Source Cancer Research
MU Faculty or unit

Faculty of Science

Citation
Web http://www.ncbi.nlm.nih.gov/pubmed/23338609
Doi http://dx.doi.org/10.1158/0008-5472.CAN-12-1752
Field Physiology
Keywords Planar cell polarity; Wnt; casein kinase 1; B-CLL
Attached files
Description 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.
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