KOZLOVÁ, Veronika, Aneta LEDEREROVÁ, Adriana LADUNGOVÁ, Helena PESCHELOVÁ, Pavlína JANOVSKÁ, A. SLUSARCZYK, J. DOMAGALA, Pavel KOPČIL, Viera VAKULOVÁ, Jan OPPELT, Vítězslav BRYJA, Michael DOUBEK, Jiří MAYER, Šárka POSPÍŠILOVÁ and Michal ŠMÍDA. CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells. Plos one. San Francisco: Public Library Science, 2020, vol. 15, No 3, p. 0229170-229189. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0229170.
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Basic information
Original name CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells
Authors KOZLOVÁ, Veronika (203 Czech Republic, belonging to the institution), Aneta LEDEREROVÁ (203 Czech Republic, belonging to the institution), Adriana LADUNGOVÁ (703 Slovakia, belonging to the institution), Helena PESCHELOVÁ (203 Czech Republic, belonging to the institution), Pavlína JANOVSKÁ (203 Czech Republic, belonging to the institution), A. SLUSARCZYK, J. DOMAGALA, Pavel KOPČIL (203 Czech Republic, belonging to the institution), Viera VAKULOVÁ (703 Slovakia, belonging to the institution), Jan OPPELT (203 Czech Republic, belonging to the institution), Vítězslav BRYJA (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Michal ŠMÍDA (203 Czech Republic, guarantor, belonging to the institution).
Edition Plos one, San Francisco, Public Library Science, 2020, 1932-6203.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30204 Oncology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 3.240
RIV identification code RIV/00216224:14740/20:00118603
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.1371/journal.pone.0229170
UT WoS 000535307600007
Keywords in English MONOCLONAL-ANTIBODY; ACTIVATION; EXPRESSION; PYK2; LYMPHOMA; MOLECULE; CHANNEL; ANTIGEN
Tags 14110212, podil, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 17/8/2020 16:05.
Abstract
Surface protein CD20 serves as the critical target of immunotherapy in various B-cell malignancies for decades, however its biological function and regulation remain largely elusive. Better understanding of CD20 function may help to design improved rational therapies to prevent development of resistance. Using CRISPR/Cas9 technique, we have abrogated CD20 expression in five different malignant B-cell lines. We show that CD20 deletion has no effect upon B-cell receptor signaling or calcium flux. Also B-cell survival and proliferation is unaffected in the absence of CD20. On the contrary, we found a strong defect in actin cytoskeleton polymerization and, consequently, defective cell adhesion and migration in response to homeostatic chemokines SDF1 alpha, CCL19 and CCL21. Mechanistically, we could identify a reduction in chemokine-triggered PYK2 activation, a calcium-activated signaling protein involved in activation of MAP kinases and cytoskeleton regulation. These cellular defects in consequence result in a severely disturbed homing of B cells in vivo.
Links
NV15-33561A, research and development projectName: Rezistence na léčbu monoklonálními protilátkami u B-CLL a B-lymfomů: příčiny vzniku a potenciální intervenční strategie
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