| Citation: | Meiyu Qu, Qiangqiang He, Hangyang Bao, Xing Ji, Tingyu Shen, Muhammad Qasim Barkat, Ximei Wu, Ling-Hui Zeng. Multiple roles of arsenic compounds in phase separation and membraneless organelles formation determine their therapeutic efficacy in tumors[J]. Journal of Pharmaceutical Analysis, 2024, 14(8): 100957. doi: 10.1016/j.jpha.2024.02.011
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Arsenic compounds are widely used for the therapeutic intervention of multiple diseases. Ancient pharmacologists discovered the medicinal utility of these highly toxic substances, and modern pharmacologists have further recognized the specific active ingredients in human diseases. In particular, Arsenic trioxide (ATO), as a main component, has therapeutic effects on various tumors (including leukemia, hepatocellular carcinoma, lung cancer, etc.). However, its toxicity limits its efficacy, and controlling the toxicity has been an important issue. Interestingly, recent evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation, which may determine their toxicity and therapeutic efficacy. Here, we summarize the arsenic compounds-regulating phase separation and membraneless organelles formation. We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds, highlighting potential mechanisms underlying the clinical application of arsenic compounds.
| [1] |
D.M. Jolliffe, A history of the use of arsenicals in man, J. R. Soc. Med. 86(1993) 287-289.
|
| [2] |
N.P. Paul, A.E. Galvan, K. Yoshinaga-Sakurai, et al., Arsenic in medicine: Past, present and future, Biometals 36(2023) 283-301.
|
| [3] |
F. Lo-Coco, G. Avvisati, M. Vignetti, et al., Retinoic acid and arsenic trioxide for acute promyelocytic leukemia, N. Engl. J. Med. 369(2013) 111-121.
|
| [4] |
T. Yoshida, H. Yamauchi, G. F. Sun, Chronic health effects in people exposed to arsenic via the drinking water: Dose-response relationships in review, Toxicol. Appl. Pharmacol. 198(2004) 243-252.
|
| [5] |
T.G. Kazi, M.B. Arain, J.A. Baig, et al., The correlation of arsenic levels in drinking water with the biological samples of skin disorders, Sci. Total Environ. 407(2009) 1019-1026.
|
| [6] |
D.N. Guha Mazumder, Effect of chronic intake of arsenic-contaminated water on liver, Toxicol. Appl. Pharmacol. 206(2005) 169-175.
|
| [7] |
A.C. Straub, D.B. Stolz, M.A. Ross, et al., Arsenic stimulates sinusoidal endothelial cell capillarization and vessel remodeling in mouse liver, Hepatology 45(2007) 205-212.
|
| [8] |
A.C. Straub, K.A. Clark, M.A. Ross, et al., Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase-generated superoxide, J. Clin. Invest. 118(2008) 3980-3989.
|
| [9] |
T. Suzuki, I. Tsukamoto, Arsenite induces apoptosis in hepatocytes through an enhancement of the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase caused by partial hepatectomy, Toxicol. Lett. 165(2006) 257-264.
|
| [10] |
L. Yu, Z. Lv, S. Li, et al., Chronic arsenic exposure induces ferroptosis via enhancing ferritinophagy in chicken livers, Sci. Total Environ. 890(2023) 164172.
|
| [11] |
L.Y. Zheng, J.G. Umans, F. Yeh, et al., The association of urine arsenic with prevalent and incident chronic kidney disease: Evidence from the Strong Heart Study, Epidemiology 26(2015) 601-612.
|
| [12] |
E.J. Tokar, R.J. Person, Y. Sun, et al., Chronic exposure of renal stem cells to inorganic arsenic induces a cancer phenotype, Chem. Res. Toxicol. 26(2013) 96-105.
|
| [13] |
Q.Q. Wang, Y.F. Lan, K. Rehman, et al., Effect of arsenic compounds on the in vitro differentiation of mouse embryonic stem cells into cardiomyocytes, Chem. Res. Toxicol. 28(2015) 351-353.
|
| [14] |
C. Douillet, J. Currier, J. Saunders, et al., Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets, Toxicol. Appl. Pharmacol. 267(2013) 11-15.
|
| [15] |
M. Huang, C. Douillet, M. Styblo, Arsenite and its trivalent methylated metabolites inhibit glucose-stimulated calcium influx and insulin secretion in murine pancreatic islets, Arch. Toxicol. 93(2019) 2525-2533.
|
| [16] |
C.H. Wang, J.S. Jeng, P.K. Yip, et al., Biological gradient between long-term arsenic exposure and carotid atherosclerosis, Circulation 105(2002) 1804-1809.
|
| [17] |
E. Hossain, K. Islam, F. Yeasmin, et al., Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic, Toxicol. Appl. Pharmacol. 259(2012) 187-194.
|
| [18] |
T.L. Tsai, W.T. Lei, C.C. Kuo, et al., Maternal and childhood exposure to inorganic arsenic and airway allergy - A 15-Year birth cohort follow-up study, Environ. Int. 146(2021), 106243.
|
| [19] |
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Some drinking-water disinfectants and contaminants, including arsenic, IARC Monogr. Eval. Carcinog. Risks Hum. 84(2004) 1-477.
|
| [20] |
A.H. Smith, M. Goycolea, R. Haque, et al., Marked increase in bladder and lung cancer mortality in a region of Northern Chile due to arsenic in drinking water, Am. J. Epidemiol. 147(1998) 660-669.
|
| [21] |
R.C. Yu, K.H. Hsu, C.J. Chen, et al., Arsenic methylation capacity and skin cancer, Cancer Epidemiol. Biomarkers Prev. 9(2000) 1259-1262.
|
| [22] |
T.D. Zhang, G.Q. Chen, Z.G. Wang, et al., Arsenic trioxide, a therapeutic agent for APL, Oncogene 20(2001) 7146-7153.
|
| [23] |
T.D. Zhang, Treatment of acute granulocytic leukemia with “Ai ling No. 1”: Clinical analysis and experimental research, Zhong Xi Yi Jie He Za Zhi 4(1984) 19-20.
|
| [24] |
G.Q. Chen, J. Zhu, X.G. Shi, et al., In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins, Blood 88(1996) 1052-1061.
|
| [25] |
H. de The, P.P. Pandolfi, Z. Chen, Acute promyelocytic leukemia: A paradigm for oncoprotein-targeted cure, Cancer Cell 32(2017) 552-560.
|
| [26] |
C. Andre, M.C. Guillemin, J. Zhu, et al., The PML and PML/RARalpha domains: From autoimmunity to molecular oncology and from retinoic acid to arsenic, Exp. Cell Res. 229(1996) 253-260.
|
| [27] |
M.H. Koken, M.T. Daniel, M. Gianni, et al., Retinoic acid, but not arsenic trioxide, degrades the PLZF/RARalpha fusion protein, without inducing terminal differentiation or apoptosis, in a RA-therapy resistant t(11;17)(q23;q21) APL patient, Oncogene 18(1999) 1113-1118.
|
| [28] |
T. Sternsdorf, E. Puccetti, K. Jensen, et al., PIC-1/SUMO-1-modified PML-retinoic acid receptor alpha mediates arsenic trioxide-induced apoptosis in acute promyelocytic leukemia, Mol. Cell Biol. 19(1999) 5170-5178.
|
| [29] |
J. Zhu, J. Zhou, L. Peres, et al., A sumoylation site in PML/RARA is essential for leukemic transformation, Cancer Cell 7(2005) 143-153.
|
| [30] |
V. Lallemand-Breitenbach, J. Zhu, Z. Chen, et al., Curing APL through PML/RARA degradation by As2O3, Trends Mol. Med. 18(2012) 36-42.
|
| [31] |
P. Isakson, M. Bjoeras, S.O. Boee, et al., Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein, Blood 116(2010) 2324-2331.
|
| [32] |
Z.H. Chen, W.T. Wang, W. Huang, et al., The lncRNA HOTAIRM1 regulates the degradation of PML-RARA oncoprotein and myeloid cell differentiation by enhancing the autophagy pathway, Cell Death Differ. 24(2017) 212-224.
|
| [33] |
J.E. Lancet, A.B. Moseley, S.E. Coutre, et al., A phase 2 study of ATRA, arsenic trioxide, and gemtuzumab ozogamicin in patients with high-risk APL (SWOG 0535), Blood Adv. 4(2020) 1683-1689.
|
| [34] |
H. Zheng, H. Jiang, S. Hu, et al., Arsenic combined with all-trans retinoic acid for pediatric acute promyelocytic leukemia: Report from the CCLG-APL2016 protocol study, J. Clin. Oncol. 39(2021) 3161-3170.
|
| [35] |
H. Gill, A.Y.H. Leung, Y.L. Kwong, Molecular and cellular mechanisms of myelodysplastic syndrome: Implications on targeted therapy, Int. J. Mol. Sci. 17(2016), 440.
|
| [36] |
Q.Q. Wang, Y. Jiang, H. Naranmandura, Therapeutic strategy of arsenic trioxide in the fight against cancers and other diseases, Metallomics 12(2020) 326-336.
|
| [37] |
A. Donelli, C. Chiodino, T. Panissidi, et al., Might arsenic trioxide be useful in the treatment of advanced myelodysplastic syndromes? Haematologica 85(2000) 1002-1003.
|
| [38] |
N. Vey, A. Bosly, A. Guerci, et al., Arsenic trioxide in patients with myelodysplastic syndromes: A phase II multicenter study, J. Clin. Oncol. 24(2006) 2465-2471.
|
| [39] |
G.J. Schiller, J. Slack, J.D. Hainsworth, et al., Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes, J. Clin. Oncol. 24(2006) 2456-2464.
|
| [40] |
N.C. Munshi, G. Tricot, R. Desikan, et al., Clinical activity of arsenic trioxide for the treatment of multiple myeloma, Leukemia 16(2002) 1835-1837.
|
| [41] |
M.A. Hussein, M. Saleh, F. Ravandi, et al., Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma, Br. J. Haematol. 125(2004) 470-476.
|
| [42] |
S. Lehmann, S. Bengtzen, A. Paul, et al., Effects of arsenic trioxide (As2O3) on leukemic cells from patients with non-M3 acute myelogenous leukemia: Studies of cytotoxicity, apoptosis and the pattern of resistance, Eur. J. Haematol. 66(2001) 357-364.
|
| [43] |
S. Parmar, L.M. Rundhaugen, L. Boehlke, et al., Phase II trial of arsenic trioxide in relapsed and refractory acute myeloid leukemia, secondary leukemia and/or newly diagnosed patients at least 65 years old, Leuk. Res. 28(2004) 909-919.
|
| [44] |
E. Negoro, T. Yamauchi, N. Fukuhara, et al., Japanese subgroup analysis in the Asian phase II study of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma, J. Clin. Exp. Hematop. 63(2023) 108-120.
|
| [45] |
S. Alarifi, D. Ali, S. Alkahtani, et al., Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells, Onco. Targets. Ther. 6(2013) 75-84.
|
| [46] |
T. Zhang, S.S. Wang, L. Hong, et al., Arsenic trioxide induces apoptosis of rat hepatocellular carcinoma cells in vivo, J. Exp. Clin. Cancer Res. 22(2003) 61-68.
|
| [47] |
C.C. Lin, C. Hsu, C.H. Hsu, et al., Arsenic trioxide in patients with hepatocellular carcinoma: A phase II trial, Invest. N. Drugs 25(2007) 77-84.
|
| [48] |
Z.Y. Shen, J. Shen, W.J. Cai, et al., The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells, Int. J. Mol. Med. 5(2000) 155-158.
|
| [49] |
Q.-S. Shao, Z.-Y. Ye, Z.-Q. Ling, et al., Cell cycle arrest and apoptotic cell death in cultured human gastric carcinoma cells mediated by arsenic trioxide, World J. Gastroenterol. 11(2005) 3451-3456.
|
| [50] |
R. Uslu, U.A. Sanli, C. Sezgin, et al., Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines, Clin. Cancer Res. 6(2000) 4957-4964.
|
| [51] |
X. Zhang, B. Hu, Y.-F. Sun, et al., Arsenic trioxide induces differentiation of cancer stem cells in hepatocellular carcinoma through inhibition of LIF/JAK1/STAT3 and NF-kB signaling pathways synergistically, Clin. Transl. Med. 11(2021), e335.
|
| [52] |
L. Li, Z. Bi, P. Wadgaonkar, et al., Metabolic and epigenetic reprogramming in the arsenic-induced cancer stem cells, Semin. Cancer Biol. 57(2019) 10-18.
|
| [53] |
X.H. Duan, S.G. Ju, X.W. Han, et al., Arsenic trioxide-eluting Callispheres beads is more effective and equally tolerant compared with arsenic trioxide/lipiodol emulsion in the transcatheter arterial chemoembolization treatment for unresectable hepatocellular carcinoma patients, Eur. Rev. Med. Pharmacol. Sci. 24(2020) 1468-1480.
|
| [54] |
D. Rongvaux-Gaida, M. Dupuis, J. Poupon, et al., High response rate and corticosteroid sparing with arsenic trioxide-based first-line therapy in chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, Transplant. Cell. Ther. 28(2022) 679.e1-679.e11.
|
| [55] |
M. Hamidou, A. Neel, J. Poupon, et al., Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: An open-label phase IIa trial (Lupsenic), Arthritis Res. Ther. 23(2021), 70.
|
| [56] |
H. Wang, Y. Liu, X. Wang, et al., Randomized clinical control study of locoregional therapy combined with arsenic trioxide for the treatment of hepatocellular carcinoma, Cancer 121(2015) 2917-2925.
|
| [57] |
G. Kchour, S.R. Rezaee, R. Farid, et al., The combination of arsenic, interferon-alpha, and zidovudine restores an “immunocompetent-like” cytokine expression profile in patients with adult T-cell leukemia lymphoma, Retrovirology 10(2013), 91.
|
| [58] |
D.H. Hoang, R. Buettner, M. Valerio, et al., Arsenic trioxide and venetoclax synergize against AML progenitors by ROS induction and inhibition of Nrf2 activation, Int. J. Mol. Sci. 23(2022), 6568.
|
| [59] |
W. Xu, C. Shu, J. Hu, et al., Effects of vitamin C combined with arsenic trioxide on the apoptosis of Hep-2 cell, Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 22(2008) 171-173.
|
| [60] |
E.P. Swindell, P.L. Hankins, H. Chen, et al., Anticancer activity of small-molecule and nanoparticulate arsenic(III) complexes, Inorg. Chem. 52(2013) 12292-12304.
|
| [61] |
R.W. Ahn, F. Chen, H. Chen, et al., A novel nanoparticulate formulation of arsenic trioxide with enhanced therapeutic efficacy in a murine model of breast cancer, Clin. Cancer Res. 16(2010) 3607-3617.
|
| [62] |
C.P. Brangwynne, C.R. Eckmann, D.S. Courson, et al., Germline P granules are liquid droplets that localize by controlled dissolution/condensation, Science 324(2009) 1729-1732.
|
| [63] |
L. Le Goff, T. Lecuit, Developmental biology. Phase transition in a cell, Science 324(2009) 1654-1655.
|
| [64] |
P. Li, S. Banjade, H.C. Cheng, et al., Phase transitions in the assembly of multivalent signalling proteins, Nature 483(2012) 336-340.
|
| [65] |
M. Kato, T.W. Han, S. Xie, et al., Cell-free formation of RNA granules: Low complexity sequence domains form dynamic fibers within hydrogels, Cell 149(2012) 753-767.
|
| [66] |
T.W. Han, M. Kato, S. Xie, et al., Cell-free formation of RNA granules: Bound RNAs identify features and components of cellular assemblies, Cell 149(2012) 768-779.
|
| [67] |
X. Tong, R. Tang, J. Xu, et al., Liquid-liquid phase separation in tumor biology, Signal Transduct. Target. Ther. 7(2022), 221.
|
| [68] |
A. Boija, I.A. Klein, R.A. Young, Biomolecular condensates and cancer, Cancer Cell 39(2021) 174-192.
|
| [69] |
S. Elbaum-Garfinkle, Y. Kim, K. Szczepaniak, et al., The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics, Proc. Natl. Acad. Sci. USA 112(2015) 7189-7194.
|
| [70] |
H. Zhang, X. Ji, P. Li, et al., Liquid-liquid phase separation in biology: Mechanisms, physiological functions and human diseases, Sci. China Life Sci. 63(2020) 953-985.
|
| [71] |
S. Alberti, A. Gladfelter, T. Mittag, Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates, Cell 176(2019) 419-434.
|
| [72] |
B. Wang, L. Zhang, T. Dai, et al., Liquid-liquid phase separation in human health and diseases, Signal Trans.Target. Ther. 6(2021), 290.
|
| [73] |
S. Boeynaems, S. Alberti, N.L. Fawzi, et al., Protein phase separation: A new phase in cell biology, Trends Cell Biol. 28(2018) 420-435.
|
| [74] |
K. You, Q. Huang, C. Yu, et al., PhaSepDB: A database of liquid-liquid phase separation related proteins, Nucleic Acids Res. 48(2020) D354-D359.
|
| [75] |
Q. Li, X. Peng, Y. Li, et al., LLPSDB: A database of proteins undergoing liquid-liquid phase separation in vitro, Nucleic Acids Res. 48(2020) D320-D327.
|
| [76] |
A.M. Navarro, F. Orti, E. Martinez-Perez, et al., DisPhaseDB: An integrative database of diseases related variations in liquid-liquid phase separation proteins, Comput. Struct. Biotechnol. J. 20(2022) 2551-2557.
|
| [77] |
M. Liu, H. Li, X. Luo, et al., RPS: A comprehensive database of RNAs involved in liquid-liquid phase separation, Nucleic Acids Res. 50(2022) D347-D355.
|
| [78] |
B. Meszaros, G. Erdős, B. Szabo, et al., PhaSePro: The database of proteins driving liquid-liquid phase separation, Nucleic Acids Res. 48(2020) D360-D367.
|
| [79] |
H. Zhu, H. Fu, T. Cui, et al., RNAPhaSep: A resource of RNAs undergoing phase separation, Nucleic Acids Res. 50(2022) D340-D346.
|
| [80] |
W. Ning, Y. Guo, S. Lin, et al., DrLLPS: A data resource of liquid-liquid phase separation in eukaryotes, Nucleic Acids Res. 48(2020) D288-D295.
|
| [81] |
S.R. Millar, J.Q. Huang, K.J. Schreiber, et al., A new phase of networking: The molecular composition and regulatory dynamics of mammalian stress granules, Chem. Rev. 123(2023) 9036-9064.
|
| [82] |
D. Piovesan, M. Necci, N. Escobedo, et al., MobiDB: Intrinsically disordered proteins in 2021, Nucleic Acids Res. 49(2021) D361-D367.
|
| [83] |
C. Hou, H. Xie, Y. Fu, et al., MloDisDB: A manually curated database of the relations between membraneless organelles and diseases, Briefings Bioinf. 22(2021), bbaa271.
|
| [84] |
A. Vandelli, M. Arnal Segura, M. Monti, et al., The PRALINE database: Protein and Rna humAn singLe nucleotIde variaNts in condEnsates, Bioinformatics 39(2023), btac847.
|
| [85] |
F. Quaglia, B. Meszaros, E. Salladini, et al., DisProt in 2022: Improved quality and accessibility of protein intrinsic disorder annotation, Nucleic Acids Res. 50(2022) D480-D487.
|
| [86] |
O.V. Galzitskaya, S.O. Garbuzynskiy, M.Y. Lobanov, FoldUnfold: Web server for the prediction of disordered regions in protein chain, Bioinformatics 22(2006) 2948-2949.
|
| [87] |
D.T. McSwiggen, M. Mir, X. Darzacq, et al., Evaluating phase separation in live cells: Diagnosis, caveats, and functional consequences, Genes Dev. 33(2019) 1619-1634.
|
| [88] |
Y. Shin, J. Berry, N. Pannucci, et al., Spatiotemporal control of intracellular phase transitions using light-activated optoDroplets, Cell 168(2017) 159-171.e14.
|
| [89] |
D. Bracha, M.T. Walls, M.T. Wei, et al., Mapping local and global liquid phase behavior in living cells using photo-oligomerizable seeds, Cell 175(2018) 1467-1480.e13.
|
| [90] |
Y. Shin, Y.-C. Chang, D.S.W. Lee, et al., Liquid nuclear condensates mechanically sense and restructure the genome, Cell 175(2018) 1481-1491.e13.
|
| [91] |
X. Zhou, Q. Hao, H. Lu, Mutant p53 in cancer therapy-the barrier or the path, J. Mol. Cell Biol. 11(2019) 293-305.
|
| [92] |
X.W. Wang, C.C. Harris, p53 tumor-suppressor gene: Clues to molecular carcinogenesis, J. Cell. Physiol. 173(1997) 247-255.
|
| [93] |
K. Kamagata, S. Kanbayashi, M. Honda, et al., Liquid-like droplet formation by tumor suppressor p53 induced by multivalent electrostatic interactions between two disordered domains, Sci. Rep. 10(2020), 580.
|
| [94] |
A. Guo, P. Salomoni, J. Luo, et al., The function of PML in p53-dependent apoptosis, Nat. Cell Biol. 2(2000) 730-736.
|
| [95] |
E.C. Petronilho, M.M. Pedrote, M.A. Marques, et al., Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands, Chem. Sci. 12(2021) 7334-7349.
|
| [96] |
L.P. Rangel, D.C.F. Costa, T.C.R.G. Vieira, et al., The aggregation of mutant p53 produces prion-like properties in cancer, Prion 8(2014) 75-84.
|
| [97] |
A.P. Ano Bom, L.P. Rangel, D.C. Costa, et al., Mutant p53 aggregates into prion-like amyloid oligomers and fibrils: Implications for cancer, J. Biol. Chem. 287(2012) 28152-28162.
|
| [98] |
A. Clark, M. Burleson, SPOP and cancer: A systematic review, Am. J. Cancer Res. 10(2020) 704-726.
|
| [99] |
M.R. Marzahn, S. Marada, J. Lee, et al., Higher-order oligomerization promotes localization of SPOP to liquid nuclear speckles, EMBO J. 35(2016) 1254-1275.
|
| [100] |
Y. Song, Y. Xu, C. Pan, et al., The emerging role of SPOP protein in tumorigenesis and cancer therapy, Mol. Cancer 19(2020), 2.
|
| [101] |
J.J. Bouchard, J.H. Otero, D.C. Scott, et al., Cancer mutations of the tumor suppressor SPOP disrupt the formation of active, phase-separated compartments, Mol. Cell. 72(2018) 19-36.e8.
|
| [102] |
D.K. Simanshu, D.V. Nissley, F. McCormick, RAS proteins and their regulators in human disease, Cell 170(2017) 17-33.
|
| [103] |
S. Li, A. Balmain, C.M. Counter, A model for RAS mutation patterns in cancers: Finding the sweet spot, Nat. Rev. Cancer 18(2018) 767-777.
|
| [104] |
K. Taniue, N. Akimitsu, Aberrant phase separation and cancer, FEBS J. 289(2022) 17-39.
|
| [105] |
E. Grabocka, D. Bar-Sagi, Mutant KRAS enhances tumor cell fitness by upregulating stress granules, Cell 167(2016) 1803-1813.e12.
|
| [106] |
K.L. Bryant, C.J. Der, Mutant RAS calms stressed-out cancer cells, Dev. Cell 40(2017) 120-122.
|
| [107] |
G. Zhu, J. Xie, W. Kong, et al., Phase separation of disease-associated SHP2 mutants underlies MAPK hyperactivation, Cell 183(2020) 490-502.e18.
|
| [108] |
J.H. Ahn, E.S. Davis, T.A. Daugird, et al., Phase separation drives aberrant chromatin looping and cancer development, Nature 595(2021) 591-595.
|
| [109] |
B. Shi, W. Li, Y. Song, et al., UTX condensation underlies its tumour-suppressive activity, Nature 597(2021) 726-731.
|
| [110] |
M. Qu, Q. He, J. Luo, et al., Sonic hedgehog signaling: Alternative splicing and pathogenic role in medulloblastoma, Genes Dis. 10(2022) 2013-2028.
|
| [111] |
H. Choudhry, A. Albukhari, M. Morotti, et al., Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival, Oncogene 34(2015), 4546.
|
| [112] |
W. Li, J. Hu, B. Shi, et al., Biophysical properties of AKAP95 protein condensates regulate splicing and tumorigenesis, Nat. Cell Biol. 22(2020) 960-972.
|
| [113] |
Y. Wu, L. Zhou, Y. Zou, et al., Disrupting the phase separation of KAT8-IRF1 diminishes PD-L1 expression and promotes antitumor immunity, Nat. Cancer 4(2023) 382-400.
|
| [114] |
M. Du, Z.J. Chen, DNA-induced liquid phase condensation of cGAS activates innate immune signaling, Science 361(2018) 704-709.
|
| [115] |
P. Pietras, A. Aulas, M.M. Fay, et al., Translation inhibition and suppression of stress granules formation by cisplatin, Biomed. Pharmacother. 145(2022), 112382.
|
| [116] |
J. Zhao, X. Fu, H. Chen, et al., G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer, Br. J. Cancer 124(2021) 425-436.
|
| [117] |
Y. Zhan, H. Wang, Y. Ning, et al., Understanding the roles of stress granule during chemotherapy for patients with malignant tumors, Am. J. Cancer Res. 10(2020) 2226-2241.
|
| [118] |
J. Xie, H. He, W. Kong, et al., Targeting androgen receptor phase separation to overcome antiandrogen resistance, Nat. Chem. Biol. 18(2022) 1341-1350.
|
| [119] |
Q. He, M. Qu, T. Shen, et al., Control of mitochondria-associated endoplasmic reticulum membranes by protein S-palmitoylation: Novel therapeutic targets for neurodegenerative diseases, Ageing Res. Rev. 87(2023), 101920.
|
| [120] |
B. Portz, B.L. Lee, J. Shorter, FUS and TDP-43 phases in health and disease, Trends Biochem. Sci. 46(2021) 550-563.
|
| [121] |
A.E. Conicella, G.H. Zerze, J. Mittal, et al., ALS mutations disrupt phase separation mediated by α-helical structure in the TDP-43 low-complexity C-terminal domain, Structure 24(2016) 1537-1549.
|
| [122] |
S. Romagnoli, A. Peris, A.R. De Gaudio, et al., SARS-CoV-2 and COVID-19: From the bench to the bedside, Physiol. Rev. 100(2020) 1455-1466.
|
| [123] |
A. Wu, Y. Peng, B. Huang, et al., Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China, Cell Host Microbe 27(2020) 325-328.
|
| [124] |
D. Kim, J.Y. Lee, J.S. Yang, et al., The architecture of SARS-CoV-2 transcriptome, Cell 181(2020) 914-921.e10.
|
| [125] |
C.R. Carlson, J.B. Asfaha, C.M. Ghent, et al., Phosphoregulation of phase separation by the SARS-CoV-2 N protein suggests a biophysical basis for its dual functions, Mol. Cell. 80(2020) 1092-1103.e4.
|
| [126] |
S. Lu, Q. Ye, D. Singh, et al., The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein, Nat. Commun. 12(2021), 502.
|
| [127] |
S.L. Soignet, S.R. Frankel, D. Douer, et al., United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia, J. Clin. Oncol. 19(2001) 3852-3860.
|
| [128] |
X.W. Zhang, X.J. Yan, Z.R. Zhou, et al., Arsenic trioxide controls the fate of the PML-RARα oncoprotein by directly binding PML, Science 328(2010) 240-243.
|
| [129] |
M. Niwa-Kawakita, O. Ferhi, H. Soilihi, et al., PML is a ROS sensor activating p53 upon oxidative stress, J. Exp. Med. 214(2017) 3197-3206.
|
| [130] |
E. Lang, A. Grudic, S. Pankiv, et al., The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling, Blood 120(2012) 847-857.
|
| [131] |
S. Hofmann, J. Mai, S. Masser, et al., ATO (arsenic trioxide) effects on promyelocytic leukemia nuclear bodies reveals antiviral intervention capacity, Adv. Sci. 7(2020), 1902130.
|
| [132] |
H.P.J. Voon, L. Hii, A. Garvie, et al., Pediatric glioma histone H3.3 K27M/G34R mutations drive abnormalities in PML nuclear bodies, Genome Biol. 24(2023), 284.
|
| [133] |
A. Petit, A. Delaune, A. Falluel-Morel, et al., Importance of ERK activation in As2O3-induced differentiation and promyelocytic leukemia nuclear bodies formation in neuroblastoma cells, Pharmacol. Res. 77(2013) 11-21.
|
| [134] |
J.Y. Dai, Y.H. Hu, Q. Niu, et al., Role of PML SUMOylation in arsenic trioxide-induced fibrosis in HSCs, Life Sci. 251(2020), 117607.
|
| [135] |
Y. Liu, D. Zhao, F. Qiu, et al., Manipulating PML SUMOylation via silencing UBC9 and RNF4 regulates cardiac fibrosis, Mol. Ther. 25(2017) 666-678.
|
| [136] |
F. Luo, Y. Zhuang, M.D. Sides, et al., Arsenic trioxide inhibits transforming growth factor-β1-induced fibroblast to myofibroblast differentiation in vitro and bleomycin induced lung fibrosis in vivo, Respir. Res. 15(2014), 51.
|
| [137] |
A.P. Ferragut Cardoso, M. Banerjee, L. Al-Eryani, et al., Temporal modulation of differential alternative splicing in HaCaT human keratinocyte cell line chronically exposed to arsenic for up to 28 wk, Environ. Health Perspect. 130(2022), 17011.
|
| [138] |
S. Singh, A.K. Pradhan, S. Chakraborty, SUMO1 negatively regulates the transcriptional activity of EVI1 and significantly increases its co-localization with EVI1 after treatment with arsenic trioxide, Biochim. Biophys. Acta 1833(2013) 2357-2368.
|
| [139] |
M. Machitani, I. Taniguchi, M. Ohno, ARS2 regulates nuclear paraspeckle formation through 3'-end processing and stability of NEAT1 long noncoding RNA, Mol. Cell Biol. 40(2020) 002699-e319.
|
| [140] |
C. Wang, Y. Duan, G. Duan, et al., Stress induces dynamic, cytotoxicity-antagonizing TDP-43 nuclear bodies via paraspeckle LncRNA NEAT1-mediated liquid-liquid phase separation, Mol. Cell. 79(2020) 443-458.e7.
|
| [141] |
C. Yang, Z. Wang, Y. Kang, et al., Stress granule homeostasis is modulated by TRIM21-mediated ubiquitination of G3BP1 and autophagy-dependent elimination of stress granules, Autophagy 19(2023) 1934-1951.
|
| [142] |
A. Turakhiya, S.R. Meyer, G. Marincola, et al., ZFAND1 recruits p97 and the 26S proteasome to promote the clearance of arsenite-induced stress granules, Mol. Cell. 70(2018) 906-919.e7.
|
| [143] |
C. Tanikawa, K. Ueda, A. Suzuki, et al., Citrullination of RGG motifs in FET proteins by PAD4 regulates protein aggregation and ALS susceptibility, Cell Rep. 22(2018) 1473-1483.
|
| [144] |
H. Li, P.H. Lin, P. Gupta, et al., MG53 suppresses tumor progression and stress granule formation by modulating G3BP2 activity in non-small cell lung cancer, Mol. Cancer 20(2021), 118.
|
| [145] |
H.Y. Chen, L.T. Lin, M.L. Wang, et al., Musashi-1 promotes chemoresistant granule formation by PKR/eIF2α signalling cascade in refractory glioblastoma, Biochim. Biophys. Acta, Mol. Basis Dis. 1864(2018) 1850-1861.
|
| [146] |
S.P. Somasekharan, F. Zhang, N. Saxena, et al., G3BP1-linked mRNA partitioning supports selective protein synthesis in response to oxidative stress, Nucleic Acids Res. 48(2020) 6855-6873.
|
| [147] |
T.A. Mason, E. Kolobova, J. Liu, et al., Darinaparsin is a multivalent chemotherapeutic which induces incomplete stress response with disruption of microtubules and Shh signaling, PLoS One 6(2011), e27699.
|
| [148] |
K. Budkina, K. El Hage, M.J. Clement, et al., YB-1 unwinds mRNA secondary structures in vitro and negatively regulates stress granule assembly in HeLa cells, Nucleic Acids Res. 49(2021) 10061-10081.
|
| [149] |
M. Takahashi, M. Higuchi, G.N. Makokha, et al., HTLV-1 Tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10, Blood 122(2013) 715-725.
|
| [150] |
T. Ohn, N. Kedersha, T. Hickman, et al., A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly, Nat. Cell Biol. 10(2008) 1224-1231.
|
| [151] |
D. Rajgor, J.A. Mellad, D. Soong, et al., Mammalian microtubule P-body dynamics are mediated by nesprin-1, J. Cell Biol. 205(2014) 457-475.
|
| [152] |
A.M. Ciancone, S. Hosseinibarkooie, D.L. Bai, et al., Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation, Cell Chem. Biol. 29(2022) 1709-1720.e7.
|
| [153] |
V. Lallemand-Breitenbach, H. de The, PML nuclear bodies: From architecture to function, Curr. Opin. Cell Biol. 52(2018) 154-161.
|
| [154] |
T. Hirose, K. Ninomiya, S. Nakagawa, et al., A guide to membraneless organelles and their various roles in gene regulation, Nat. Rev. Mol. Cell Biol. 24(2023) 288-304.
|
| [155] |
Y. Li, X. Ma, W. Wu, et al., PML nuclear body biogenesis, carcinogenesis, and targeted therapy, Trends Cancer 6(2020) 889-906.
|
| [156] |
Y.T. Wang, J. Chen, C.W. Chang, et al., Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment, J. Clin. Invest. 127(2017) 2982-2997.
|
| [157] |
H. de The, C. Chomienne, M. Lanotte, et al., The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus, Nature 347(1990) 558-561.
|
| [158] |
P. Salomoni, B.J. Ferguson, A.H. Wyllie, et al., New insights into the role of PML in tumour suppression, Cell Res. 18(2008) 622-640.
|
| [159] |
E.L. Reineke, Y. Liu, H.Y. Kao, Promyelocytic leukemia protein controls cell migration in response to hydrogen peroxide and insulin-like growth factor-1, J. Biol. Chem. 285(2010) 9485-9492.
|
| [160] |
R. Bernardi, I. Guernah, D. Jin, et al., PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR, Nature 442(2006) 779-785.
|
| [161] |
A. Carracedo, D. Weiss, A.K. Leliaert, et al., A metabolic prosurvival role for PML in breast cancer, J. Clin. Invest. 122(2012) 3088-3100.
|
| [162] |
K. Wiesmeijer, C. Molenaar, I.M.L.A. Bekeer, et al., Mobile foci of Sp100 do not contain PML: PML bodies are immobile but PML and Sp100 proteins are not, J. Struct. Biol. 140(2002) 180-188.
|
| [163] |
M. Jeanne, V. Lallemand-Breitenbach, O. Ferhi, et al., PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3, Cancer Cell 18(2010) 88-98.
|
| [164] |
E. Goto, A. Tomita, F. Hayakawa, et al., Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment, Blood 118(2011) 1600-1609.
|
| [165] |
P. Wang, S. Benhenda, H. Wu, et al., RING tetramerization is required for nuclear body biogenesis and PML sumoylation, Nat. Commun. 9(2018), 1277.
|
| [166] |
S. Chakraborty, V. Senyuk, S. Sitailo, et al., Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles, J. Biol. Chem. 276(2001) 44936-44943.
|
| [167] |
D.L. Spector, A.I. Lamond, Nuclear speckles, Cold Spring Harb. Perspect. Biol. 3(2011), a000646.
|
| [168] |
N. Saitoh, C.S. Spahr, S.D. Patterson, et al., Proteomic analysis of interchromatin granule clusters, Mol. Biol. Cell 15(2004) 3876-3890.
|
| [169] |
X.D. Fu, T. Maniatis, Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus, Nature 343(1990) 437-441.
|
| [170] |
X.D. Fu, T. Maniatis, Isolation of a complementary DNA that encodes the mammalian splicing factor SC35, Science 256(1992) 535-538.
|
| [171] |
J. Kim, K.Y. Han, N. Khanna, et al., Nuclear speckle fusion via long-range directional motion regulates speckle morphology after transcriptional inhibition, J. Cell Sci. 132(2019), jcs.226563.
|
| [172] |
I.A. Ilik, M. Malszycki, A.K. Lubke, et al., SON and SRRM2 are essential for nuclear speckle formation, Elife 9(2020), e60579.
|
| [173] |
Q. Zhang, K.P. Kota, S.G. Alam, et al., Coordinated dynamics of RNA splicing speckles in the nucleus, J. Cell. Physiol. 231(2016) 1269-1275.
|
| [174] |
Y. Chen, A.S. Belmont, Genome organization around nuclear speckles, Curr. Opin. Genet. Dev. 55(2019) 91-99.
|
| [175] |
S.A. Quinodoz, N. Ollikainen, B. Tabak, et al., Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus, Cell 174(2018) 744-757.e24.
|
| [176] |
M. Banerjee, A.P. Ferragut Cardoso, A. Lykoudi, et al., Arsenite exposure displaces zinc from ZRANB2 leading to altered splicing, Chem. Res. Toxicol. 33(2020) 1403-1417.
|
| [177] |
A.H. Fox, S. Nakagawa, T. Hirose, et al., Paraspeckles: Where long noncoding RNA meets phase separation, Trends Biochem. Sci. 43(2018) 124-135.
|
| [178] |
A.H. Fox, Y.W. Lam, A.K. Leung, et al., Paraspeckles: A novel nuclear domain, Curr. Biol. 12(2002) 13-25.
|
| [179] |
Y.T.F. Sasaki, T. Ideue, M. Sano, et al., MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles, Proc. Natl. Acad. Sci. USA 106(2009) 2525-2530.
|
| [180] |
T. Naganuma, S. Nakagawa, A. Tanigawa, et al., Alternative 3'-end processing of long noncoding RNA initiates construction of nuclear paraspeckles, EMBO J. 31(2012) 4020-4034.
|
| [181] |
C.M. Clemson, J.N. Hutchinson, S.A. Sara, et al., An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles, Mol. Cell. 33(2009) 717-726.
|
| [182] |
D. Chakravarty, A. Sboner, S.S. Nair, et al., The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer, Nat. Commun. 5(2014), 5383.
|
| [183] |
C. Adriaens, L. Standaert, J. Barra, et al., p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity, Nat. Med. 22(2016) 861-868.
|
| [184] |
L. Cui, C. Gao, R.D. Zhang, et al., Low expressions of ARS2 and CASP8AP2 predict relapse and poor prognosis in pediatric acute lymphoblastic leukemia patients treated on China CCLG-ALL 2008 protocol, Leuk. Res. 39(2015) 115-123.
|
| [185] |
D.S.W. Protter, R. Parker, Principles and properties of stress granules, Trends Cell Biol. 26(2016) 668-679.
|
| [186] |
S. Hofmann, N. Kedersha, P. Anderson, et al., Molecular mechanisms of stress granule assembly and disassembly, Biochim. Biophys. Acta Mol. Cell Res. 1868(2021), 118876.
|
| [187] |
P. Ivanov, N. Kedersha, P. Anderson, Stress granules and processing bodies in translational control, Cold Spring Harb. Perspect. Biol. 11(2019), a032813.
|
| [188] |
S.A. Wek, S. Zhu, R.C. Wek, The histidyl-tRNA synthetase-related sequence in the eIF-2 alpha protein kinase GCN2 interacts with tRNA and is required for activation in response to starvation for different amino acids, Mol. Cell Biol. 15(1995) 4497-4506.
|
| [189] |
S.P. Srivastava, K.U. Kumar, R.J. Kaufman, Phosphorylation of eukaryotic translation initiation factor 2 mediates apoptosis in response to activation of the double-stranded RNA-dependent protein kinase, J. Biol. Chem. 273(1998) 2416-2423.
|
| [190] |
H.P. Harding, Y. Zhang, A. Bertolotti, et al., Perk is essential for translational regulation and cell survival during the unfolded protein response, Mol. Cell. 5(2000) 897-904.
|
| [191] |
M. Cadena Sandoval, A.M. Heberle, U. Rehbein, et al., mTORC1 crosstalk with stress granules in aging and age-related Diseases, Front. Aging 2(2021), 761333.
|
| [192] |
M. Ganassi, D. Mateju, I. Bigi, et al., A surveillance function of the HSPB8-BAG3-HSP70 chaperone complex ensures stress granule integrity and dynamism, Mol. Cell. 63(2016) 796-810.
|
| [193] |
J.R. Buchan, R.M. Kolaitis, J.P. Taylor, et al., Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function, Cell 153(2013) 1461-1474.
|
| [194] |
B. Wolozin, P. Ivanov, Stress granules and neurodegeneration, Nat. Rev. Neurosci. 20(2019) 649-666.
|
| [195] |
T. Hu, W. Hou, E. Xiao, et al., Mechanism and effect of stress granule formation in cancer and its potential roles in breast cancer therapy, Genes Dis. 9(2021) 659-667.
|
| [196] |
S. Fang, X. Wan, X. Zou, et al., Arsenic trioxide induces macrophage autophagy and atheroprotection by regulating ROS-dependent TFEB nuclear translocation and AKT/mTOR pathway, Cell Death Dis. 12(2021), 88.
|
| [197] |
P. Wadgaonkar, F. Chen, Connections between endoplasmic reticulum stress-associated unfolded protein response, mitochondria, and autophagy in arsenic-induced carcinogenesis, Semin. Cancer Biol. 76(2021) 258-266.
|
| [198] |
Y. Li, J. Peng, Y. Xia, et al., Sufu limits sepsis-induced lung inflammation via regulating phase separation of TRAF6, Theranostics 13(2023) 3761-3780.
|
| [199] |
B. Nsengimana, F.A. Khan, E.E. Ngowi, et al., Processing body (P-body) and its mediators in cancer, Mol. Cell. Biochem. 477(2022) 1217-1238.
|
| [200] |
T. Eystathioy, E.K. Chan, S.A. Tenenbaum, et al., A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique population of human mRNAs within novel cytoplasmic speckles, Mol. Biol. Cell 13(2002) 1338-1351.
|
| [201] |
U. Sheth, R. Parker, Decapping and decay of messenger RNA occur in cytoplasmic processing bodies, Science 300(2003) 805-808.
|
| [202] |
S.A. Fromm, V. Truffault, J. Kamenz, et al., The structural basis of Edc3- and Scd6-mediated activation of the Dcp1: Dcp2 mRNA decapping complex, EMBO J. 31(2012) 279-290.
|
| [203] |
C.J. Decker, D. Teixeira, R. Parker, Edc3p and a glutamine/asparagine-rich domain of Lsm4p function in processing body assembly in Saccharomyces cerevisiae, J. Cell Biol. 179(2007) 437-449.
|
| [204] |
S.D. Hardy, A. Shinde, W.H. Wang, et al., Regulation of epithelial-mesenchymal transition and metastasis by TGF-β, P-bodies, and autophagy, Oncotarget 8(2017) 103302-103314.
|
| [205] |
E.C. Little, E.R. Camp, C. Wang, et al., The CaSm (LSm1) oncogene promotes transformation, chemoresistance and metastasis of pancreatic cancer cells, Oncogenesis 5(2016), e182.
|
| [206] |
S. Takahashi, S. Suzuki, S. Inaguma, et al., Down-regulation of Lsm1 is involved in human prostate cancer progression, Br. J. Cancer 86(2002) 940-946.
|
| [207] |
A. Serman, F. Le Roy, C. Aigueperse, et al., GW body disassembly triggered by siRNAs independently of their silencing activity, Nucleic Acids Res. 35(2007) 4715-4727.
|
| [208] |
A. Vennemann, T.G. Hofmann, SUMO regulates proteasome-dependent degradation of FLASH/Casp8AP2, Cell Cycle 12(2013) 1914-1921.
|
| [209] |
X.C. Yang, I. Sabath, L. Kunduru, et al., A conserved interaction that is essential for the biogenesis of histone locus bodies, J. Biol. Chem. 289(2014) 33767-33782.
|
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