The planar cell polarity pathway drives pathogenesis of chronic lymphocytic leukemia by the regulation of B-lymphocyte migration.

نویسندگان

  • Markéta Kaucká
  • Karla Plevová
  • Sárka Pavlová
  • Pavlína Janovská
  • Archana Mishra
  • Jan Verner
  • Jirina Procházková
  • Pavel Krejcí
  • Jana Kotasková
  • Petra Ovesná
  • Boris Tichy
  • Yvona Brychtová
  • Michael Doubek
  • Alois Kozubík
  • Jirí Mayer
  • Sárka Pospísilová
  • Vítezslav Bryja
چکیده

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)-ε 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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عنوان ژورنال:
  • Cancer research

دوره 73 5  شماره 

صفحات  -

تاریخ انتشار 2013