The planar cell polarity pathway drives pathogenesis of chronic lymphocytic leukemia by the regulation of B-lymphocyte migration.
نویسندگان
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.
منابع مشابه
Analysis of HLA-G Gene Expression in B-Lymphocytes from Chronic Lymphocytic Leukemia Patients
The human leukocyte antigen G (HLA-G) molecule exhibits limited tissue distribution, low polymorphism and alternative splicings that generate seven HLA-G isoforms. HLA-G exerts multiple immunoregulatory functions. Recent studies indicate an ectopic up-regulation in tumor cells that may favor their escape from anti-tumor immune responses. This study it is an effort to clarify the presence of HLA...
متن کاملChronic lymphocytic leukemia, biology, new diagnosis and treatment: review article
Chronic lymphocytic leukemia (CLL) is a malignancy of B CD5+cells and is the most common type of leukemia in adults. The disease is more common in men over 50 years in western countries. CLL is associated with defective apoptosis in B cells. CLL was traditionally regarded as a disease that occurs before naïve B cells meet the antigen in the lymph nodes. Laboratory diagnosis requires white blood...
متن کاملComparison Cytotoxic Effects of Mangifera Indica L. and Juglans Regia Aqueous Extract on Human Chronic Lymphocytic Leukemia
Natural products isolated from plant sources are well known for their pharmacological potential in diversity of disease treatments such as inflammatory or cancer conditions. Mango (Mangifera indica L.) and Juglans regia are thought to be rich of functional phytochemicals. To elucidate the anticancer activity of Juglans regia (JR) and Mangifera indica L (MI) aqueous extract were investigated on ...
متن کاملExpression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia
Chronic lymphocytic leukemia is a disease with up-regulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic ly...
متن کاملInvestigation of SMAD3 and SMAD4 genes expression in CML patients and K562 cell line and association with chronic myeloid leukemia
Aim and Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with cytogenetic characterization of the abnormal Philadelphia chromosome. This chromosome results from a reciprocal translocation between chromosomes 9 and 22. This is an important signaling pathway in the process of cancer cell proliferation and apoptosis, as well as the pathogenesis of TGF-β disease, i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cancer research
دوره 73 5 شماره
صفحات -
تاریخ انتشار 2013