Dysregulation of TNFα-induced necroptotic signaling in chronic lymphocytic leukemia: suppression of CYLD gene by LEF1 - PubMed (original) (raw)
. 2012 Jun;26(6):1293-300.
doi: 10.1038/leu.2011.357. Epub 2011 Dec 13.
B Xu, W Shen, H Zhu, W Wu, Y Fu, H Chen, H Dong, Y Zhu, K Miao, W Xu, J Li
Affiliations
- PMID: 22157808
- DOI: 10.1038/leu.2011.357
Dysregulation of TNFα-induced necroptotic signaling in chronic lymphocytic leukemia: suppression of CYLD gene by LEF1
P Liu et al. Leukemia. 2012 Jun.
Abstract
Impaired cell death program has been noted as one of the hallmarks of chronic lymphocytic leukemia (CLL) and contributes to its accumulation of malignant monoclonal B cells as well as to chemotherapy resistance. A cell can die through the apoptosis or necrosis pathway. Recent investigations suggest that in apoptotic-deficient conditions, such as most types of cancer, a process of programmed necrosis, called necroptosis, prevails. However, the detailed molecular mechanisms underlying this alternative cell death pathway are still not fully understood. Here we demonstrate that CLL cells failed to undergo necroptosis upon stimulation of TNFα combined with pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD). Two core components of necroptotic machine, RIP3 and deubiquitinase cylindromatosis (CYLD), are markedly downregulated in CLL. Moreover, we identified lymphoid enhancer-binding factor 1 (LEF1), a downstream effector of the Wnt/β-catenin pathway, as a transcription repressor of CYLD in CLL. Knocking down LEF1 sensitizes CLL cells to TNFα/zVAD-induced necroptosis. The present investigation provides the first evidence that CLL cells have defects not only in apoptotic program but also in necroptotic signaling. Targeting the key regulators of necroptotic machine, such as LEF1, to restore this pathway may represent a novel approach for CLL treatment.
Similar articles
- High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia and may be targeted by ethacrynic acid.
Wu W, Zhu H, Fu Y, Shen W, Miao K, Hong M, Xu W, Fan L, Young KH, Liu P, Li J. Wu W, et al. Oncotarget. 2016 Apr 19;7(16):21631-43. doi: 10.18632/oncotarget.7795. Oncotarget. 2016. PMID: 26950276 Free PMC article. - Reactive oxygen species regulate Smac mimetic/TNFα-induced necroptotic signaling and cell death.
Schenk B, Fulda S. Schenk B, et al. Oncogene. 2015 Nov 19;34(47):5796-806. doi: 10.1038/onc.2015.35. Epub 2015 Apr 6. Oncogene. 2015. PMID: 25867066 - Methylprednisolone suppresses the Wnt signaling pathway in chronic lymphocytic leukemia cell line MEC-1 regulated by LEF-1 expression.
Yao QM, Li PP, Liang SM, Lu K, Zhu XJ, Liu YX, Zhang F, Yuan T, Wang X. Yao QM, et al. Int J Clin Exp Pathol. 2015 Jul 1;8(7):7921-8. eCollection 2015. Int J Clin Exp Pathol. 2015. PMID: 26339357 Free PMC article. - Wnt/β-catenin/LEF-1 signaling in chronic lymphocytic leukemia (CLL): a target for current and potential therapeutic options.
Gandhirajan RK, Poll-Wolbeck SJ, Gehrke I, Kreuzer KA. Gandhirajan RK, et al. Curr Cancer Drug Targets. 2010 Nov;10(7):716-27. doi: 10.2174/156800910793605794. Curr Cancer Drug Targets. 2010. PMID: 20578984 Review. - Necroptosis: an emerging form of programmed cell death.
Wu W, Liu P, Li J. Wu W, et al. Crit Rev Oncol Hematol. 2012 Jun;82(3):249-58. doi: 10.1016/j.critrevonc.2011.08.004. Epub 2011 Oct 1. Crit Rev Oncol Hematol. 2012. PMID: 21962882 Review.
Cited by
- Deregulation of New Cell Death Mechanisms in Leukemia.
Favale G, Donnarumma F, Capone V, Della Torre L, Beato A, Carannante D, Verrilli G, Nawaz A, Grimaldi F, De Simone MC, Del Gaudio N, Megchelenbrink WL, Caraglia M, Benedetti R, Altucci L, Carafa V. Favale G, et al. Cancers (Basel). 2024 Apr 25;16(9):1657. doi: 10.3390/cancers16091657. Cancers (Basel). 2024. PMID: 38730609 Free PMC article. Review. - Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity.
Meier P, Legrand AJ, Adam D, Silke J. Meier P, et al. Nat Rev Cancer. 2024 May;24(5):299-315. doi: 10.1038/s41568-024-00674-x. Epub 2024 Mar 7. Nat Rev Cancer. 2024. PMID: 38454135 Review. - Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.
Hou Y, Yu W, Wu G, Wang Z, Leng S, Dong M, Li N, Chen L. Hou Y, et al. Cell Death Dis. 2023 Aug 8;14(8):510. doi: 10.1038/s41419-023-06024-3. Cell Death Dis. 2023. PMID: 37553362 Free PMC article. - Global publication trends and research trends of necroptosis application in tumor: A bibliometric analysis.
Wu YY, Li CC, Lin X, Xu F, Shan SK, Guo B, Li FX, Zheng MH, Xu QS, Lei LM, Duan JY, Tang KX, Cao YC, Yuan LQ. Wu YY, et al. Front Pharmacol. 2023 Apr 24;14:1112484. doi: 10.3389/fphar.2023.1112484. eCollection 2023. Front Pharmacol. 2023. PMID: 37169000 Free PMC article. - SREBP activation contributes to fatty acid accumulations in necroptosis.
Lu D, Parisi LR, Gokcumen O, Atilla-Gokcumen GE. Lu D, et al. RSC Chem Biol. 2023 Feb 13;4(4):310-322. doi: 10.1039/d2cb00172a. eCollection 2023 Apr 5. RSC Chem Biol. 2023. PMID: 37034406 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous