Combined inhibition/silencing of diacylglycerol kinase α and ζ simultaneously and synergistically enhances interleukin-2 production in T cells and induces cell death of melanoma cells.
T cell
anticancer immunity
apoptosis
cancer
diacylglycerol kinase
interleukin-2
Journal
Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
13
11
2020
received:
10
10
2020
accepted:
18
11
2020
pubmed:
6
1
2021
medline:
5
10
2021
entrez:
5
1
2021
Statut:
ppublish
Résumé
The α-isozyme of diacylglycerol kinase (DGK) enhances cancer cell proliferation and, conversely, it promotes the nonresponsive immune state known as T-cell anergy. Moreover, a DGKα-selective inhibitor, CU-3, induced cell death in cancer-derived cells and simultaneously enhanced T-cell interleukin-2 production. In addition to DGKα, DGKζ is also known to induce T-cell anergy. In the present study, we examined whether combined inhibition/silencing of DGKα and DGKζ synergistically enhanced T-cell activity. Combined treatment with CU-3 or DGKα-small interfering RNA (siRNA) and DGKζ-siRNA more potently enhanced T-cell receptor-crosslink-dependent interleukin-2 production in Jurkat T cells than treatment with either alone. Intriguingly, in addition to activating T cells, dual inhibition/silencing of DGKα and DGKζ synergistically reduced viability and increased caspase 3/7 activity in AKI melanoma cells. Taken together, these results indicate that combined inhibition/silencing of DGKα and DGKζ simultaneously and synergistically enhances interleukin-2 production in T cells and induces cell death in melanoma. Therefore, dual inhibition/silencing of these DGK isozymes represents an ideal therapy that potently attenuates cancer cell proliferation and simultaneously enhances immune responses that impact anticancer immunity.
Substances chimiques
Interleukin-2
0
Diacylglycerol Kinase
EC 2.7.1.107
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
494-506Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Goto K, Hozumi Y, Kondo H. Diacylglycerol, phosphatidic acid, and the converting enzyme, diacylglycerol kinase, in the nucleus. Biochim Biophys Acta. 2006;1761(5-6):535-541. https://doi.org/10.1016/j.bbalip.2006.04.001
Merida I, Avila-Flores A, Merino E. Diacylglycerol kinases: at the hub of cell signalling. Biochem J. 2008;409(1):1-18. https://doi.org/10.1042/BJ20071040
Sakane F, Imai S, Kai M, Yasuda S, Kanoh H. Diacylglycerol kinases: why so many of them? Biochim Biophys Acta. 2007;1771(7):793-806. https://doi.org/10.1016/j.bbalip.2007.04.006
Sakane F, Mizuno S, Takahashi D, Sakai H. Where do substrates of diacylglycerol kinases come from? Diacylglycerol kinases utilize diacylglycerol species supplied from phosphatidylinositol turnover-independent pathways. Adv Biol Regul. 2018;67:101-108. https://doi.org/10.1016/j.jbior.2017.09.003
Topham MK, Epand RM. Mammalian diacylglycerol kinases: molecular interactions and biological functions of selected isoforms. Biochim Biophys Acta. 2009;1790(6):416-424. https://doi.org/10.1016/j.bbagen.2009.01.010
Goto K, Kondo H. Molecular cloning and expression of a 90-kDa diacylglycerol kinase that predominantly localizes in neurons. Proc Natl Acad Sci USA. 1993;90(16):7598-7602. https://doi.org/10.1073/pnas.90.16.7598
Kai M, Sakane F, Imai S, Wada I, Kanoh H. Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in human retina with a truncated and inactive enzyme expression in most other human cells. J Biol Chem. 1994;269(28):18492-18498.
Sakane F, Yamada K, Kanoh H, Yokoyama C, Tanabe T. Porcine diacylglycerol kinase sequence has zinc finger and E-F hand motifs. Nature. 1990;344(6264):345-348. https://doi.org/10.1038/344345a0
Schaap D, de Widt J, van der Wal J, et al. Purification, cDNA-cloning and expression of human diacylglycerol kinase. FEBS Lett. 1990;275(1-2):151-158. https://doi.org/10.1016/0014-5793(90)81461-V
Goto K, Funayama M, Kondo H. Cloning and expression of a cytoskeleton-associated diacylglycerol kinase that is dominantly expressed in cerebellum. Proc Natl Acad Sci USA. 1994;91(26):13042-13046. https://doi.org/10.1073/pnas.91.26.13042
Goto K, Kondo H. A 104-kDa diacylglycerol kinase containing ankyrin-like repeats localizes in the cell nucleus. Proc Natl Acad Sci USA. 1996;93(20):11196-11201.
Bunting M, Tang W, Zimmerman GA, McIntyre TM, Prescott SM. Molecular cloning and characterization of a novel human diacylglycerol kinase ζ. J Biol Chem. 1996;271(17):10230-10236.
Ding L, Traer E, McIntyre TM, Zimmerman GA, Prescott SM. The cloning and characterization of a novel human diacylglycerol kinase, DGKι. J Biol Chem. 1998;273(49):32746-32752.
Goto K, Nakano T, Hozumi Y. Diacylglycerol kinase and animal models: the pathophysiological roles in the brain and heart. Adv Enzyme Regul. 2006;46:192-202. https://doi.org/10.1016/j.advenzreg.2006.01.005
Merida I, Torres-Ayuso P, Avila-Flores A, et al. Diacylglycerol kinases in cancer. Adv Biol Regul. 2017;63:22-31. https://doi.org/10.1016/j.jbior.2016.09.005
Sakane F, Imai S, Kai M, Yasuda S, Kanoh H. Diacylglycerol kinases as emerging potential drug targets for a variety of diseases. Curr Drug Targets. 2008;9(8):626-640. https://doi.org/10.2174/138945008785132394
Sakane F, Mizuno S, Komenoi S. Diacylglycerol kinases as emerging potential drug targets for a variety of diseases: an update. Front Cell Dev Biol. 2016;4:82. https://doi.org/10.3389/fcell.2016.00082
Baldanzi G, Ragnoli B, Malerba M. Potential role of diacylglycerol kinases in immune-mediated diseases. Clin Sci (Lond). 2020;134(13):1637-1658. https://doi.org/10.1042/CS20200389
Shirai Y, Saito N. Diacylglycerol kinase as a possible therapeutic target for neuronal diseases. J Biomed Sci. 2014;21:28. https://doi.org/10.1186/1423-0127-21-28
Takeishi K, Taketomi A, Shirabe K, et al. Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway. J Hepatol. 2012;57(1):77-83. https://doi.org/10.1016/j.jhep.2012.02.026
Yanagisawa K, Yasuda S, Kai M, et al. Diacylglycerol kinase α suppresses tumor necrosis factor-α-induced apoptosis of human melanoma cells through NF-κB activation. Biochim Biophys Acta. 2007;1771(4):462-474. https://doi.org/10.1016/j.bbalip.2006.12.008
Kai M, Yasuda S, Imai S, Toyota M, Kanoh H, Sakane F. Diacylglycerol kinase α enhances protein kinase Cζ-dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-κB. FEBS Lett. 2009;583(19):3265-3268. https://doi.org/10.1016/j.febslet.2009.09.017
Baldanzi G, Mitola S, Cutrupi S, et al. Activation of diacylglycerol kinase α is required for VEGF-induced angiogenic signaling in vitro. Oncogene. 2004;23(28):4828-4838. https://doi.org/10.1038/sj.onc.1207633
Rainero E, Caswell PT, Muller PA, et al. Diacylglycerol kinase alpha controls RCP-dependent integrin trafficking to promote invasive migration. J Cell Biol. 2012;196(2):277-295. https://doi.org/10.1083/jcb.201109112
Sato M, Liu K, Sasaki S, et al. Evaluations of the selectivities of the diacylglycerol kinase inhibitors R59022 and R59949 among diacylglycerol kinase isozymes using a new non-radioactive assay method. Pharmacology. 2013;92(1-2):99-107. https://doi.org/10.1159/000351849
Dominguez CL, Floyd DH, Xiao A, et al. Diacylglycerol kinase α is a critical signaling node and novel therapeutic target in glioblastoma and other cancers. Cancer Discov. 2013;3(7):782-797. https://doi.org/10.1158/2159-8290.cd-12-0215
Yamada K, Sakane F, Kanoh H. Immunoquantitation of 80 kDa diacylglycerol kinase in pig and human lymphocytes and several other cells. FEBS Lett. 1989;244(2):402-406.
Olenchock BA, Guo R, Carpenter JH, et al. Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. Nat Immunol. 2006;7(11):1174-1181. https://doi.org/10.1038/ni1400
Zha Y, Marks R, Ho AW, et al. T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-α. Nat Immunol. 2006;7(11):1166-1173. https://doi.org/10.1038/ni1394
Foell J, Hewes B, Mittler RS. T cell costimulatory and inhibitory receptors as therapeutic targets for inducing anti-tumor immunity. Curr Cancer Drug Targets. 2007;7(1):55-70. https://doi.org/10.2174/156800907780006841
Prinz PU, Mendler AN, Masouris I, Durner L, Oberneder R, Noessner E. High DGK-alpha and disabled MAPK pathways cause dysfunction of human tumor-infiltrating CD8+ T cells that is reversible by pharmacologic intervention. J Immunol. 2012;188(12):5990-6000. https://doi.org/10.4049/jimmunol.1103028
Merida I, Andrada E, Gharbi SI, Avila-Flores A. Redundant and specialized roles for diacylglycerol kinases alpha and zeta in the control of T cell functions. Sci Signal. 2015;8(374):re6. https://doi.org/10.1126/scisignal.aaa0974
Noessner E. DGK-alpha: a checkpoint in cancer-mediated immuno-inhibition and target for immunotherapy. Front Cell Dev Biol. 2017;5:16. https://doi.org/10.3389/fcell.2017.00016
Riese MJ, Moon EK, Johnson BD, Albelda SM. Diacylglycerol kinases (dgks): novel targets for improving T cell activity in cancer. Front Cell Dev Biol. 2016;4:108. https://doi.org/10.3389/fcell.2016.00108
Liu K, Kunii N, Sakuma M, et al. A novel diacylglycerol kinase α-selective inhibitor, CU-3, induces cancer cell apoptosis and enhances immune response. J Lipid Res. 2016;57(3):368-379. https://doi.org/10.1194/jlr.M062794
Yamaki A, Akiyama R, Murakami C, et al. Diacylglycerol kinase alpha-selective inhibitors induce apoptosis and reduce viability of melanoma and several other cancer cell lines. J Cell Biochem. 2019;120(6):10043-10056. https://doi.org/10.1002/jcb.28288
Riese MJ, Grewal J, Das J, et al. Decreased diacylglycerol metabolism enhances ERK activation and augments CD8+ T cell functional responses. J Biol Chem. 2011;286(7):5254-5265. https://doi.org/10.1074/jbc.M110.171884
Singh BK, Kambayashi T. The immunomodulatory functions of diacylglycerol kinase zeta. Front Cell Dev Biol. 2016;4:96. https://doi.org/10.3389/fcell.2016.00096
Avila-Flores A, Santos T, Rincon E, Merida I. Modulation of the mammalian target of rapamycin pathway by diacylglycerol kinase-produced phosphatidic acid. J Biol Chem. 2005;280(11):10091-10099.
Tanaka S, Akaishi E, Hosaka K, Okamura S, Kubohara Y. Zinc ions suppress mitogen-activated interleukin-2 production in Jurkat cells. Biochem Biophys Res Commun. 2005;335(1):162-167. https://doi.org/10.1016/j.bbrc.2005.07.059
Purow B. Molecular pathways: targeting diacylglycerol kinase alpha in cancer. Clin Cancer Res. 2015;21(22):5008-5012. https://doi.org/10.1158/1078-0432.CCR-15-0413
Jung IY, Kim YY, Yu HS, Lee M, Kim S, Lee J. CRISPR/Cas9-mediated knockout of DGK improves antitumor activities of human T cells. Cancer Res. 2018;78(16):4692-4703. https://doi.org/10.1158/0008-5472.CAN-18-0030
Riese MJ, Wang LC, Moon EK, et al. Enhanced effector responses in activated CD8+ T cells deficient in diacylglycerol kinases. Cancer Res. 2013;73(12):3566-3577. https://doi.org/10.1158/0008-5472.CAN-12-3874
Guo R, Wan CK, Carpenter JH, et al. Synergistic control of T cell development and tumor suppression by diacylglycerol kinase α and ζ. Proc Natl Acad Sci USA. 2008;105(33):11909-11914. https://doi.org/10.1073/pnas.0711856105
Arranz-Nicolas J, Ogando J, Soutar D, et al. Diacylglycerol kinase alpha inactivation is an integral component of the costimulatory pathway that amplifies TCR signals. Cancer Immunol Immunother. 2018;67(6):965-980. https://doi.org/10.1007/s00262-018-2154-8
Jones DR, Sanjuan MA, Stone JC, Merida I. Expression of a catalytically inactive form of diacylglycerol kinase alpha induces sustained signaling through RasGRP. FASEB J. 2002;16(6):595-597.
Zhong XP, Hainey EA, Olenchock BA, et al. Enhanced T cell responses due to diacylglycerol kinase ζ deficiency. Nat Immunol. 2003;4(9):882-890.
Sakane F, Hoshino F, Murakami C. New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein. Int J Mol Sci. 2020;21(18):E6794. https://doi.org/10.3390/ijms21186794
Murakami Y, Murakami C, Hoshino F, et al. Palmitic acid- and/or palmitoleic acid-containing phosphatidic acids are generated by diacylglycerol kinase α in starved Jurkat T cells. Biochem Biophys Res Commun. 2020;525(4):1054-1060.
Olmez I, Love S, Xiao A, et al. Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha. Neuro Oncol. 2018;20(2):192-202. https://doi.org/10.1093/neuonc/nox119
Velnati S, Massarotti A, Antona A, et al. Structure activity relationship studies on Amb639752: toward the identification of a common pharmacophoric structure for DGKalpha inhibitors. J Enzyme Inhib Med Chem. 2020;35(1):96-108. https://doi.org/10.1080/14756366.2019.1684911