Selective Inhibition of IκB Kinase Sensitizes Mantle Cell Lymphoma B Cells to TRAIL by Decreasing Cellular FLIP Level
作者： Gaël Roué , Patricia Pérez-Galán , Mónica López-Guerra , Neus Villamor , Elias Campo
DOI: 10.4049/JIMMUNOL.178.3.1923
关键词: Apoptosis 、 Cytotoxic T cell 、 Immunology 、 Caspase 、 Cell culture 、 IκB kinase 、 Cancer research 、 Medicine 、 Bortezomib 、 Gene knockdown 、 Flip
摘要: In an attempt to circumvent the intrinsic resistance of mantle cell lymphoma (MCL) cells apoptosis, we have analyzed their sensitivity extrinsic apoptotic signal triggered by TRAIL. We show here that TRAIL can trigger apoptosis in a majority MCL lines and primary cultures, irrespective receptor levels, Bcl-2 family members, or caspase regulator expression. was closely linked activity NF-κB p50 factor consequent expression cellular FLIP (c-FLIP), which accumulated into TRAIL-dependent complex resistant cells. c-FLIP transient knockdown overcame TRAIL, while inhibitors differentially modulated cytotoxicity. Indeed, bortezomib increased cytotoxic effects sensitive cells, but led intracellular accumulation c-FLIP, impeding full synergistic interaction. contrast, IκB kinase inhibitor BMS-345541 decreased allowed all samples undergo TRAIL-mediated apoptosis. These results present combination stimulation inhibition as new approach therapy.
pubpeer.com参考文章(40)
Dolors Colomer, Elias Campo, Itziar Salaverria, Patricia Perez-Galan, Mantle cell lymphoma: from pathology and molecular pathogenesis to new therapeutic perspectives Haematologica. ,vol. 91, pp. 11- 16 ,(2006) , 10.3324/%X
Henning Walczak, Robert E. Miller, Kiley Ariail, Brian Gliniak, Thomas S. Griffith, Marek Kubin, Wilson Chin, Jon Jones, Anne Woodward, Tiep Le, Craig Smith, Pam Smolak, Raymond G. Goodwin, Charles T. Rauch, JoAnn C.L. Schuh, David H. Lynch, Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo Nature Medicine. ,vol. 5, pp. 157- 163 ,(1999) , 10.1038/5517
V Bottero, S Withoff, I M Verma, NF-κB and the regulation of hematopoiesis Cell Death & Differentiation. ,vol. 13, pp. 785- 797 ,(2006) , 10.1038/SJ.CDD.4401888
N D Perkins, T D Gilmore, Good cop, bad cop: the different faces of NF-κB Cell Death & Differentiation. ,vol. 13, pp. 759- 772 ,(2006) , 10.1038/SJ.CDD.4401838
Dario C. Altieri, Anthony D. Sandler, Takeo Azuhata, David L. Scott, Nathan R. Wall, Jonathan M. Fialkov, Thomas S. Griffith, Richard D. Williams, Induction and Regulation of Tumor Necrosis Factor-related Apoptosis-inducing Ligand/Apo-2 Ligand-mediated Apoptosis in Renal Cell Carcinoma Cancer Research. ,vol. 62, pp. 3093- 3099 ,(2002)
Hajime Higuchi, Jung-Hwan Yoon, Annette Grambihler, Nathan Werneburg, Steven F. Bronk, Gregory J. Gores, Bile Acids Stimulate cFLIP Phosphorylation Enhancing TRAIL-mediated Apoptosis Journal of Biological Chemistry. ,vol. 278, pp. 454- 461 ,(2003) , 10.1074/JBC.M209387200
Chang Xiao, Bao Feng Yang, Neda Asadi, Francesco Beguinot, Chunhai Hao, Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells. Journal of Biological Chemistry. ,vol. 277, pp. 25020- 25025 ,(2002) , 10.1074/JBC.M202946200
Xi Yi Zhang, Xu Dong Zhang, Jodie M. Borrow, Tam Nguyen, Peter Hersey, Translational control of tumor necrosis factor-related apoptosis-inducing ligand death receptor expression in melanoma cells. Journal of Biological Chemistry. ,vol. 279, pp. 10606- 10614 ,(2004) , 10.1074/JBC.M308211200
Jérôme Kucharczak, Matthew J Simmons, Yongjun Fan, Céline Gélinas, To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis. Oncogene. ,vol. 22, pp. 8961- 8982 ,(2003) , 10.1038/SJ.ONC.1207230
Sankar Ghosh, Michael Karin, Missing Pieces in the NF-κB Puzzle Cell. ,vol. 109, pp. S81- S96 ,(2002) , 10.1016/S0092-8674(02)00703-1