Open Access Review

The Dual Roles of S-Nitrosylation of Proteins in Cancer: Molecular Mechanisms and Recent Advancements

by Yi Wu a,1 ,  Yanqi Li a,1 ,  Tong Wu a  and  Hongmei Yang a,* orcid
a
The Public Experimental Center, Changchun University of Chinese Medicine, Changchun 130117, China
*
Author to whom correspondence should be addressed.
CI  2024 3(2):37; https://doi.org/10.58567/ci03020005
Received: 1 January 2024 / Accepted: 27 February 2024 / Published Online: 1 March 2024
View Full-Text
Download PDF

Abstract

Protein S-nitrosylation (SNO), emerging as an important posttranslational modification, involves covalent addition of nitric oxide (NO) to the sulfur atom of cysteine in proteins. Accumulated evidence suggests that protein SNO plays crucial roles in pathophysiological mechanisms in cancer, which is attracting great attention. However, there are still controversies about whether S-nitrosylated proteins act as oncogenic proteins or tumor suppressors in cancer. In this review, we provide an overview of the early and latest evidence regarding the underlying mechanism and dual roles of SNO in cancer, in an effort to clarify its contribution in tumor progression. It has been well established that S-nitrosylated proteins restrain tumor progression in several types of cancer, while they have exhibited activities in promoting cell proliferation and inhibiting apoptosis in some other kinds of cancer. Interestingly, emerging evidence also has highlighted both its anti-cancer and pro-tumorigenic roles in several other cancer diseases. Finally, current limitations and future research prospects are presented. The overview of targeting SNO in cancer will provide new opportunities for drug development through in-depth exploration of SNO-mediated signaling pathways.

Keywords: Protein S-nitrosylation; Cancer; Restraining tumor; Inhibiting apoptosis; Signaling pathway;
Copyright: © 2024 by Wu, Li, Wu and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funding

the Science and Technology Development Planning Project of Jilin Province (No. 20220508086RC, No. 20230203157SF)

Share and Cite

ACS Style
Wu, Y.; Li, Y.; Wu, T.; Yang, H. The Dual Roles of S-Nitrosylation of Proteins in Cancer: Molecular Mechanisms and Recent Advancements. Cancer Insight, 2024, 3, 37. https://doi.org/10.58567/ci03020005
AMA Style
Wu Y, Li Y, Wu T, Yang H. The Dual Roles of S-Nitrosylation of Proteins in Cancer: Molecular Mechanisms and Recent Advancements. Cancer Insight; 2024, 3(2):37. https://doi.org/10.58567/ci03020005
Chicago/Turabian Style
Wu, Yi; Li, Yanqi; Wu, Tong; Yang, Hongmei 2024. "The Dual Roles of S-Nitrosylation of Proteins in Cancer: Molecular Mechanisms and Recent Advancements" Cancer Insight 3, no.2:37. https://doi.org/10.58567/ci03020005
APA style
Wu, Y., Li, Y., Wu, T., & Yang, H. (2024). The Dual Roles of S-Nitrosylation of Proteins in Cancer: Molecular Mechanisms and Recent Advancements. Cancer Insight, 3(2), 37. https://doi.org/10.58567/ci03020005

Article Metrics

Article Access Statistics

References

  1. Deo, SVS., Sharma, J., and Kumar, S. (2022). GLOBOCAN 2020 Report on Global Cancer Burden: Challenges and Opportunities for Surgical Oncologists. Ann Surg Oncol 29(11), 6497-6500. https://doi.org/10.1245/s10434-022-12151-6
  2. Sung, H., Ferlay, J., and Siegel, RL. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71(3), 209-249. https://doi.org/10.3322/caac.21660
  3. Maomao, C., He, L., and Dianqin, S. (2022). Current cancer burden in China: epidemiology, etiology, and prevention. Cancer Biol Med 19(8), 1121–38. https://doi.org/10.20892/j.issn.2095-3941.2022.0231
  4. Lewandowska, AM., Rudzki, M., and Rudzki, S. (2019). Environmental risk factors for cancer - review paper. Ann Agric Environ Med 26(1), 1-7. https://doi.org/10.26444/aaem/94299
  5. Song, Y., Xu, Y., and Pan, C. (2022). The emerging role of SPOP protein in tumorigenesis and cancer therapy. Mol Cancer 19(1), 2. https://doi.org/10.1186/s12943-019-1124-x
  6. Yu, F., Yu, C., and Li, F. (2021). Wnt/β-catenin signaling in cancers and targeted therapies. Signal Transduct Target Ther 6(1),307. https://doi.org/10.1038/s41392-021-00701-5
  7. Pan, S., and Chen, R. (2022). Pathological implication of protein post-translational modifications in cancer. Mol Aspects Med 86, 101097. https://doi.org/10.1016/j.mam.2022.101097
  8. Plenchette, S., Romagny, S., and Laurens, V. (2016). Itinéraire d'un agent double - NO, S-nitrosylation et cancer [NO and cancer: itinerary of a double agent]. Med Sci (Paris) 32(6-7), 625-33. https://doi.org/10.1051/medsci/20163206027
  9. Hickok, JR., and Thomas, DD. (2010). Nitric oxide and cancer therapy: the emperor has NO clothes. Curr Pharm Des 16(4), 381-91. https://doi.org/10.2174/138161210790232149
  10. Aranda, E., López-Pedrera, C., and De, La Haba-Rodriguez. (2012). Nitric oxide and cancer: the emerging role of S-nitrosylation. Curr Mol Med 12(1), 50-67. https://doi.org/10.2174/156652412798376099
  11. Sharma, V., Fernando, V., and Letson, J. (2021). S-Nitrosylation in Tumor Microenvironment. Int J Mol Sci 22(9), 4600. https://doi.org/10.3390/ijms22094600
  12. Mishra, D., Patel, V., and Banerjee, D. (2020). Nitric Oxide and S-Nitrosylation in Cancers: Emphasis on Breast Cancer. Breast Cancer (Auckl) 14, 1178223419882688. https://doi.org/10.1177/1178223419882688
  13. Ramírez-Patiño, R., Avalos-Navarro, and G., Figuera, LE. (2022). Influence of nitric oxide signaling mechanisms in cancer. Int J Immunopathol Pharmacol 36, 3946320221135454. https://doi.org/10.1177/03946320221135454
  14. Ye, H., Wu, J., and Liang, Z. (2022). Protein S-Nitrosation: Biochemistry, Identification, Molecular Mechanisms, and Therapeutic Applications. J Med Chem 65(8), 5902-5925. https://doi.org/10.1021/acs.jmedchem.1c02194
  15. Zhang, Y., Deng, Y., and Yang, X. (2022). The Relationship Between Protein S-Nitrosylation and Human Diseases: A Review. Neurochem Res 45(12), 2815-2827. https://doi.org/10.1007/s11064-020-03136-6
  16. Wynia-Smith, SL., and Smith, BC. (2017). Nitrosothiol formation and S-nitrosation signaling through nitric oxide synthases. Nitric Oxide 63, 52-60. https://doi.org/10.1016/j.niox.2016.10.001
  17. Numajiri, N., Takasawa, K., and Nishiya, T. (2011). On-off system for PI3-kinase-Akt signaling through S-nitrosylation of phosphatase with sequence homology to tensin (PTEN). Proc Natl Acad Sci U S A 108(25), 10349-54. https://doi.org/10.1073/pnas.1103503108
  18. Wang, Z. (2012). Protein S-nitrosylation and cancer. Cancer Lett 320(2), 123-9. https://doi.org/10.1016/j.canlet.2012.03.009
  19. Marozkina, NV., and Gaston, B. (2012). S-Nitrosylation signaling regulates cellular protein interactions. Biochim Biophys Acta 1820(6), 722-9. https://doi.org/10.1016/j.bbagen.2011.06.017
  20. Khatib, S., Artoul, F., and Gershko, M. (2014). The synthesis and analysis of S-nitorsylated paraoxonase 1. Biochem Biophys Res Commun 444(3), 354-9. https://doi.org/10.1016/j.bbrc.2014.01.042
  21. Rizza, S., and Filomeni, G. (2020). Exploiting S-nitrosylation for cancer therapy: facts and perspectives. Biochem J 477(19), 3649-3672. https://doi.org/10.1042/BCJ20200064
  22. Peskin, AV., Meotti, FC., and de Souza, LF. (2020). Intra-dimer cooperativity between the active site cysteines during the oxidation of peroxiredoxin 2. Free Radic Biol Med 158, 115-125. https://doi.org/10.1016/j.freeradbiomed.2020.07.007
  23. Zhang, Y., Sun, C., and Xiao, G. (2019). S-nitrosylation of the Peroxiredoxin-2 promotes S-nitrosoglutathione-mediated lung cancer cells apoptosis via AMPK-SIRT1 pathway. Cell Death Dis 10(5), 329. https://doi.org/10.1038/s41419-019-1561-x
  24. Zhou, S., Han, Q., and Wang, R. (2016). PRDX2 protects hepatocellular carcinoma SMMC-7721 cells from oxidative stress. Oncol Lett 12(3), 2217-2221. https://doi.org/10.3892/ol.2016.4899
  25. Barnett, SD., and Buxton, ILO. (2017). The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy. Crit Rev Biochem Mol Biol 52(3), 340-354. https://doi.org/10.1080/10409238.2017.1304353
  26. Marozkina, NV., Wei, C., and Yemen, S. (2012). S-nitrosoglutathione reductase in human lung cancer. Am J Respir Cell Mol Biol 46(1), 63-70. https://doi.org/10.1165/rcmb.2011-0147OC
  27. Broniowska, KA., Diers, AR., and Hogg, N. (2013). S-nitrosoglutathione. Biochim Biophys Acta 1830(5), 3173-81. https://doi.org/10.1016/j.bbagen.2013.02.004
  28. Wang, Z., Wang, N., and Liu, P. (2016). AMPK and Cancer. Exp Suppl 107, 203-226. https://doi.org/10.1007/978-3-319-43589-3_9
  29. Lee, CW., Wong, LL., and Tse, EY. (2012). AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res 72(17), 4394-404. https://doi.org/10.1158/0008-5472.CAN-12-0429
  30. Poillet-Perez, L., Despouy, G., and Delage-Mourroux, R. (2010). Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy. Redox Biol 4, 184-92. https://doi.org/10.1016/j.redox.2014.12.003
  31. Achard, V., Putora, PM., and Omlin, A. (2012). Metastatic Prostate Cancer: Treatment Options. Oncology 100(1), 48-59. https://doi.org/10.1159/000519861
  32. Hench, IB., Cathomas, R., and Costa, L. (2019). Analysis of AR/ARV7Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial). Cancers (Basel) 11(8), 1099. https://doi.org/10.3390/cancers11081099
  33. Metcalf, D. (2013). The colony-stimulating factors and cancer. Cancer Immunol Res 1(6), 351-6. https://doi.org/10.1158/2326-6066.CIR-13-0151
  34. Hamilton, JA., Cook, AD., and Tak, PP. (2016). Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases. Nat Rev Drug Discov 16(1), 53-70. https://doi.org/10.1038/nrd.2016.231
  35. Sehgal, A., Irvine, KM., and Hume, DA. (2021). Functions of macrophage colony-stimulating factor (CSF1) in development, homeostasis, and tissue repair. Semin Immunol 54, 101509. https://doi.org/10.1016/j.smim.2021.101509
  36. Magkouta, SF., Vaitsi, PC., and Pappas, AG. (2021). CSF1/CSF1R Blockade Limits Mesothelioma and Enhances Efficiency of Anti-PDL1Immunotherapy. Cancers (Basel) 13(11), 2546. https://doi.org/10.3390/cancers13112546
  37. Firdaus, F., Kuchakulla, M., and Qureshi, R. (2022) S-nitrosylation of CSF1 receptor increases the efficacy of CSF1R blockage against prostate cancer. Cell Death Dis 13(10), 859. https://doi.org/10.1038/s41419-022-05289-4
  38. Zheng, L., Yang, Q., and Li, F. (2022). The Glycosylation of Immune Checkpoints and Their Applications in Oncology. Pharmaceuticals (Basel) 15(12),1451. https://doi.org/10.3390/ph15121451
  39. Labianca, R., Beretta, GD., and Kildani, B. (2010). Colon cancer. Crit Rev Oncol Hematol 74(2), 106-33. https://doi.org/10.1016/j.critrevonc.2010.01.010
  40. Zadoroznyj, A., and Dubrez, L. (2022). Cytoplasmic and Nuclear Functions of cIAP1. Biomolecules 12(2), 322. https://doi.org/10.3390/biom12020322
  41. Akizuki, Y., Morita, M., and Mori, Y. (2022). cIAP1-based degraders induce degradation via branched ubiquitin architectures. Nat Chem Biol 19(3), 311-322. https://doi.org/10.1038/s41589-022-01178-1
  42. Varfolomeev, E., Blankenship, JW., and Wayson, SM. (2007). IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 131(4), 669-81. https://doi.org/10.1016/j.cell.2007.10.030
  43. Hira, K., Sajeli, and Begum, A. (2021). Methods for Evaluation of TNF-α Inhibition Effect. Methods Mol Biol 2248:271-279. https://doi.org/10.1007/978-1-0716-1130-2_21
  44. Brenner, D., Blaser, H., and Mak, TW. (2015). Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol 15(6), 362-74. https://doi.org/10.1038/nri3834
  45. Romagny, S., Bouaouiche, and S., Lucchi, G. (2018). S-Nitrosylation of cIAP1 Switches Cancer Cell Fate from TNFα/TNFR1-Mediated Cell Survival to Cell Death. Cancer Res 78(8), 1948-1957. https://doi.org/10.1158/0008-5472.CAN-17-2078
  46. Motolani, A., Martin, M., and Sun, M. (2020). Phosphorylation of the Regulators, a Complex Facet of NF-κB Signaling in Cancer. Biomolecules 11(1), 15. https://doi.org/10.3390/biom11010015
  47. Varfolomeev, E., and Vucic, D. (2022). RIP1 post-translational modifications. Biochem J 479(9), 929-951. https://doi.org/10.1042/BCJ20210725
  48. Nakamura, T., Wang, L., and Wong, CC. (2010). Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death. Mol Cell 39(2), 184-95. https://doi.org/10.1016/j.molcel.2010.07.002
  49. Brigle, K., and Rogers, B. (2017). Pathobiology and Diagnosis of Multiple Myeloma. Semin Oncol Nurs 33(3), 225-236. https://doi.org/10.1016/j.soncn.2017.05.012
  50. Kim, J., Choi, S., and Saxena, N. (2017). Regulation of STAT3 and NF-κB activations by S-nitrosylation in multiple myeloma. Free Radic Biol Med 106, 245-253. https://doi.org/10.1016/j.freeradbiomed.2017.02.039
  51. Zou, S., Tong, Q., and Liu, B. (2020). Targeting STAT3 in Cancer Immunotherapy. Mol Cancer 19(1), 145. https://doi.org/10.1186/s12943-020-01258-7
  52. Guanizo, AC., Fernando, CD., and Garama, DJ. (2018). STAT3: a multifaceted oncoprotein. Growth Factors 36(1-2), 1-14. https://doi.org/10.1080/08977194.2018.1473393
  53. Manni, S., Brancalion, A., and Mandato, E. (2013). Protein kinase CK2 inhibition down modulates the NF-κB and STAT3 survival pathways, enhances the cellular proteotoxic stress and synergistically boosts the cytotoxic effect of bortezomib on multiple myeloma and mantle cell lymphoma cells. PLoS One 8(9), e75280. https://doi.org/10.1371/journal.pone.0075280
  54. Ma, J., Gong, W., and Liu, S. (2018). Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-κB and STAT3. Tumour Biol 40(1), 1010428317731369. https://doi.org/10.1177/1010428317731369
  55. Kannaiyan, R., Hay, HS., and Rajendran, P. (2011). Celastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-κB and STAT3 regulated gene products in multiple myeloma cells. Br J Pharmacol 164(5), 1506-21. https://doi.org/10.1111/j.1476-5381.2011.01449.x
  56. Bharti, AC., Shishodia, S., and Reuben, JM. (2004). Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood 103(8), 3175-84. https://doi.org/10.1182/blood-2003-06-2151
  57. Bommert, K., Bargou, RC., and Stühmer, T. (2006). Signalling and survival pathways in multiple myeloma. Eur J Cancer 42(11), 1574-80. https://doi.org/10.1016/j.ejca.2005.12.026
  58. Kim, J., Choi, S., and Saxena, N. (2017). Regulation of STAT3 and NF-κB activations by S-nitrosylation in multiple myeloma. Free Radic Biol Med 106, 245-253. https://doi.org/10.1016/j.freeradbiomed.2017.02.039
  59. Bhattacharya, S., Ray, RM., and Johnson, LR. (2005). STAT3-mediated transcription of Bcl-2, Mcl-1 and c-IAP2 prevents apoptosis in polyamine-depleted cells. Biochem J 392(Pt 2), 335-44. https://doi.org/10.1042/BJ20050465
  60. Siegel RL, Miller KD, Jemal A. (2018). Cancer statistics,2018. CA: a cancer journal for clinicians 68, 7-30. https://doi.org/10.3322/caac.21442
  61. Theoharides TC, Kempuraj D. (2023). Potential Role of Moesin in Regulating Mast Cell Secretion. International Journal of Molecular Sciences 24(15):12081. https://pubmed.ncbi.nlm.nih.gov/37569454/.2023
  62. Solinet S, Mahmud K, Stewman SF, Ben El Kadhi K, Decelle B, Talje L, et al. (2013). The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex. International Journal of Molecular Sciences 202(2) 251-260. https://doi.org/10.1083/jcb.201304052
  63. Blanchoin L, Boujemaa-Paterski R, Sykes C, Plastino J. (2014). Actin dynamics, architecture, and mechanics in cell motility. Physiological Reviews 94: 235-63. https://doi.org/10.1152/physrev.00018.2013
  64. Bouchet, BP., and Akhmanova, A. (2017). Microtubules in 3D cell motility. J Cell Sci 130(1), 39-50. https://doi.org/10.1242/jcs.189431
  65. Succony, L., Rassl, DM., and Barker, AP. (2021). Adenocarcinoma spectrum lesions of the lung: Detection, pathology and treatment strategies. Cancer Treat Rev 99, 102237. https://doi.org/10.1016/j.ctrv.2021.102237
  66. Apte, RS., Chen, DS., and Ferrara, N. (2019). VEGF in Signaling and Disease: Beyond Discovery and Development. Cell 176(6), 1248-1264. https://doi.org/10.1016/j.cell.2019.01.021
  67. Zhang, C., Li, T., and Yin, S. (2022). Monocytes deposit migrasomes to promote embryonic angiogenesis. Nat Cell Biol 24(12), 1726-1738. https://doi.org/10.1038/s41556-022-01026-3
  68. Byzova, TV., Goldman, CK., and Jankau, J. (2002). Adenovirus encoding vascular endothelial growth factor-D induces tissue-specific vascular patterns in vivo. Blood 99(12). 4434-42. https://doi.org/10.1182/blood.v99.12.4434
  69. Ehrenfeld, P., Cordova, F., and Duran, WN. (2019). S-nitrosylation and its role in breast cancer angiogenesis and metastasis. Nitric Oxide 87, 52-59. https://doi.org/10.1016/j.niox.2019.03.002
  70. Kowalczuk, O., Laudanski, J., and Laudanski, W. (2018). Lymphatics-associated genes are downregulated at transcription level in non-small cell lung cancer. Oncol Lett 15(5), 6752-6762. https://doi.org/10.3892/ol.2018.8159
  71. He, Q., Qu, M., and Shen, T. (2022). Suppression of VEGFD expression by S-nitrosylation promotes the development of lung adenocarcinoma. J Exp Clin Cancer Res 41(1), 239. https://doi.org/10.1186/s13046-022-02453-8
  72. Dhillon, J., and Betancourt, M. (2020). Pancreatic Ductal Adenocarcinoma. Monogr Clin Cytol 26, 74-91. https://doi.org/10.1159/000455736
  73. Adamska, A., Domenichini, A., and Falasca, M. (2017). Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies. Int J Mol Sci 18(7), 1338. https://doi.org/10.3390/ijms18071338
  74. Vincent, A., Herman, J., and Schulick, R. (2011). Pancreatic cancer. Lancet 378(9791), 607-20. https://doi.org/10.1016/S0140-6736(10)62307-0
  75. Cheng, H., Wang, L., and Mollica, M. (2014). Nitric oxide in cancer metastasis. Cancer Lett 353(1), 1-7. https://doi.org/10.1016/j.canlet.2014.07.014
  76. Salimian, Rizi, B., Achreja, A., and Nagrath, D. (2017). Nitric Oxide: The Forgotten Child of Tumor Metabolism. Trends Cancer 3(9), 659-672. https://doi.org/10.1016/j.trecan.2017.07.005
  77. Seth, D., and Stamler, JS. (2011). The SNO-proteome: causation and classifications. Curr Opin Chem Biol 15(1), 129-36. https://doi.org/10.1016/j.cbpa.2010.10.012
  78. Tan, C., Li, Y., and Huang, X. (2019). Extensive protein S-nitrosylation associated with human pancreatic ductal adenocarcinoma pathogenesis. Cell Death Dis 10(12), 914. https://doi.org/10.1038/s41419-019-2144-6
  79. Lim, KH., Ancrile, BB., and Kashatus, DF. (2008). Tumour maintenance is mediated by eNOS. Nature 452(7187), 646-9. https://doi.org/10.1038/nature06778
  80. Jin, UH., Karki, K., and Kim, SB. (2018). Inhibition of pancreatic cancer Panc1 cellmigration by omeprazole is dependent on aryl hydrocarbon receptor activation of JNK. Biochem Biophys Res Commun 501(3), 751-757. https://doi.org/10.1016/j.bbrc.2018.05.061
  81. Aimé, S., Hichami, S., and Wendehenne, D. (2018). Analysis of Recombinant Protein S-Nitrosylation Using the Biotin-Switch Technique. Methods Mol Biol 1747, 131-141. https://doi.org/10.1007/978-1-4939-7695-9_11
  82. Li, X., Ramadori, P., and Pfister, D. (2021). The immunological and metabolic landscape in primary and metastatic liver cancer. Nat Rev Cancer 21(9), 541-557. https://doi.org/10.1038/s41568-021-00383-9
  83. Perz, JF., Armstrong, GL., and Farrington, LA. (2006). The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45(4), 529-38. https://doi.org/10.1016/j.jhep.2006.05.013
  84. Farazi, PA., and DePinho, RA. (2006). Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 6(9), 674-87. https://doi.org/10.1038/nrc1934
  85. Rizza, S., Montagna, C., and Cardaci, S. (2006). S-nitrosylation of the Mitochondrial Chaperone TRAP1 Sensitizes Hepatocellular Carcinoma Cells to Inhibitors of Succinate Dehydrogenase. Cancer Res 76(14), 4170-82. https://doi.org/10.1158/0008-5472.CAN-15-2637
  86. Liu, Q., Gu, T., and Su, LY. (2021). GSNOR facilitates antiviral innate immunity by restricting TBK1 cysteine S-nitrosation. Redox Biol 47, 102172. https://doi.org/10.1016/j.redox.2021.102172
  87. Barnett, SD., and Buxton, ILO. (2017). The role of S-nitrosoglutathione reductase (GSNOR) in human disease and therapy. Crit Rev Biochem Mol Biol 52(3), 340-354. https://doi.org/10.1080/10409238.2017.1304353
  88. Rizza, S., Di, Leo., and L, Pecorari. (2023). GSNOR deficiency promotes tumor growth via FAK1 S-nitrosylation. Cell Rep 42(1), 111997. https://doi.org/10.1016/j.celrep.2023.111997
  89. Hess, DT., Matsumoto, A., and Kim, SO. (2005). Protein S-nitrosylation: purview and parameters. Nat Rev Mol Cell Biol 6(2), 150-66. https://doi.org/10.1038/nrm1569
  90. Wei, W., Li, B., and Hanes, MA. (2010). S-nitrosylation from GSNOR deficiency impairs DNA repair and promotes hepatocarcinogenesis. Sci Transl Med 2(19), 19ra13. https://doi.org/10.1126/scitranslmed.3000328
  91. Lu, H., Cassis, LA., and Kooi, CW. (2016). Structure and functions of angiotensinogen. Hypertens Res 39(7), 492-500. https://doi.org/10.1038/hr.2016.17
  92. Tubbs, JL., Pegg, AE., and Tainer, JA. (2007). DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy. DNA Repair (Amst) 6(8), 1100-15. https://doi.org/10.1016/j.dnarep.2007.03.011
  93. Wei, W., Yang, Z., and Tang, CH. (2011). Targeted deletion of GSNOR inhepatocytes of mice causes nitrosative inactivation of O6-alkylguanine-DNA alkyltransferase and increased sensitivity to genotoxic diethylnitrosamine. Carcinogenesis 32(7), 973-7. https://doi.org/10.1093/carcin/bgr041
  94. Lv, H., Zhu, C., and Wei, W. (2020). Enhanced Keap1-Nrf2/Trx-1 axis by daphnetin protects against oxidative stress-driven hepatotoxicity via inhibiting ASK1/JNK and Txnip/NLRP3 inflammasome activation. Phytomedicine 71, 153241. https://doi.org/10.1016/j.phymed.2020.153241
  95. Yu, C., and Xiao, JH. (2021). The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging. Oxid Med Cell Longev, 6635460. https://doi.org/10.1155/2021/6635460
  96. Quinti, L., Dayalan, Naidu S., Träger, U. (2017). KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients. Proc Natl Acad Sci U S A 114(23), E4676-E4685. https://doi.org/10.1073/pnas.1614943114
  97. Xinastle-Castillo, LO., and Landa, A. (2022). Physiological and modulatory role of thioredoxins in the cellular function. Open Med (Wars) 17(1), 2021-2035. https://doi.org/10.1515/med-2022-0596
  98. González, R., Rodríguez-Hernández, MA., and Negrete, M. (2020). Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer. Redox Biol 34, 101528. https://doi.org/10.1016/j.redox.2020.101528
  99. Oberacker, T., Kraft, L., and Schanz, M. (2023). The Importance of Thioredoxin-1 in Health and Disease. Antioxidants (Basel) 12(5), 1078. https://doi.org/10.3390/antiox12051078
  100. Chen, W., Wei, W., and Yu, L. (2021). Mammary Development and Breast Cancer: a Notch Perspective. J Mammary Gland Biol Neoplasia 26(3), 309-320. https://doi.org/10.1007/s10911-021-09496-1
  101. Shao, S., Zhao, X., and Zhang, X. (2015). Notch1 signaling regulates the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner. Mol Cancer 14(1), 28. https://doi.org/10.1186/s12943-015-0295-3
  102. Mishra, D., Patel, V., and Banerjee, D. (2020). Nitric Oxide and S-Nitrosylation in Cancers: Emphasis on Breast Cancer. Breast Cancer (Auckl) 14, 1178223419882688. https://doi.org/10.1177/1178223419882688
  103. Buggy, Y., Maguire, TM., and McGreal, G. (2004). Overexpression of the Ets-1 transcription factor in human breast cancer. Br J Cancer 91(7), 1308-15. https://doi.org/10.1038/sj.bjc.6602128
  104. Mylona, EE., Alexandrou, PT., and Giannopouloum IA. (2006). Study of the topographic distribution of ets-1 protein expression in invasive breast carcinomas in relation to tumor phenotype. Cancer Detect Prev 30(2), 111-7. https://doi.org/10.1016/j.cdp.2006.03.006
  105. Switzer, CH., Cheng, RY., and Ridnour, LA. (2012). Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast Cancer Res 14(5), R125. https://doi.org/10.1186/bcr3319
  106. Marshall, HE., and Foster, MW. (2012). S-nitrosylation of Ras in breast cancer. Breast Cancer Res 14(6), 113. https://doi.org/10.1186/bcr3331
  107. Switzer, CH., Glynn, SA., and Cheng, RY. (2012). S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer. Mol Cancer Res 10(9), 1203-15. https://doi.org/10.1158/1541-7786.MCR-12-0124
  108. Rashid, M., Zadeh, LR., and Baradaran, B. (2021). Up-down regulation of HIF-1α in cancer progression. Gene 798, 145796. https://doi.org/10.1016/j.gene.2021.145796
  109. Li, F., Sonveaux, P., and Rabbani, ZN. (2007). Regulation of HIF-1alpha stability through S-nitrosylation. Mol Cell 26(1), 63-74. https://doi.org/10.1016/j.molcel.2007.02.024
  110. Mittal, K., Ebos, J., and Rini, B. (2014). Angiogenesis and the tumor microenvironment: vascular endothelial growth factor and beyond. Semin Oncol 41(2), 235-51. https://doi.org/10.1053/j.seminoncol.2014.02.007
  111. Kobayashi, M., Narumi, K., and Furugen, A. (2021). Transport function, regulation, and biology of human monocarboxylate transporter 1 (hMCT1) and 4 (hMCT4). Pharmacol Ther 226, 107862. https://doi.org/10.1016/j.pharmthera.2021.107862
  112. Stewart, C., Ralyea, C., and Lockwood, S. (2019). Ovarian Cancer: An Integrated Review. Semin Oncol Nurs 35(2), 151-156. https://doi.org/10.1016/j.soncn.2019.02.001
  113. Ganapathy-Kanniappan, S., and Geschwind, JF. (2013). Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer 12, 152. https://doi.org/10.1186/1476-4598-12-152
  114. Yi, W., Clark, PM., and Mason, DE. (2012). Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337(6097), 975-80. https://doi.org/10.1126/science.1222278
  115. Firestein, BL., and Bredt, DS. (1999). Interaction of neuronal nitric-oxide synthase and phosphofructokinase-M. J Biol Chem 274(15), 10545-50. https://doi.org/10.1074/jbc.274.15.10545
  116. Gao, W., Huang, M., and Chen, X. (2021). The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells. Cell Death Dis 12(4), 408. https://doi.org/10.1038/s41419-021-03681-0
  117. Sawa, T., and Ohshima, H. (2006). Nitrative DNA damage in inflammation and its possible role in carcinogenesis. Nitric Oxide 14(2), 91-100. https://doi.org/10.1016/j.niox.2005.06.005
  118. Burke, AJ., Garrido, P., and Johnson, C. (2017). Inflammation and Nitrosative Stress Effects in Ovarian and Prostate Pathology and Carcinogenesis. Antioxid Redox Signal 26(18), 1078-1090. https://doi.org/10.1089/ars.2017.7004
  119. Furuhashi, S., Sugita, H., Takamori, H. (2012). NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells. Int J Oncol 40(3), 807-15. https://doi.org/10.3892/ijo.2011.1243
  120. Giri, S., Rattan, R., and Deshpande, M. (2014). Preclinical therapeutic potential of a nitrosylating agent in the treatment of ovarian cancer. PLoS One 9(6), e97897. https://doi.org/10.1371/journal.pone.0097897
  121. Liu, M., Wang, F., and Wen, Z. (2014). Blockage of STAT3 signaling pathway with a decoy oligodeoxynucleotide inhibits growth of human ovarian cancer cells. Cancer Invest 32(1), 8-12. https://doi.org/10.3109/07357907.2013.861471
  122. Altomare, DA., Wang, HQ., and Skele, KL. (2004). AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth. Oncogene 23(34), 5853-7. https://doi.org/10.1038/sj.onc.1207721
  123. Qin, Y., Dey, A., and Daaka, Y. (2013). Protein s-nitrosylation measurement. Methods Enzymol 522:409-25. https://doi.org/10.1016/B978-0-12-407865-9.00019-4
  124. Glish, GL., Vachet, RW. (2003). The basics of mass spectrometry in the twenty-first century. Nat Rev Drug Discov 2(2):140-50. https://doi.org/10.1038/nrd1011
  125. Raju, K., Doulias, PT., and Tenopoulou, M. (2012). Strategies and tools to explore protein S-nitrosylation. Biochim Biophys Acta 1820(6):684-8. https://doi.org/10.1016/j.bbagen.2011.05.009
  126. Bhattacharyya, C., Chakraborty, S., and Sengupta, R. (2022). NO news: S-(de)nitrosylation of cathepsins and their relationship with cancer. Anal Biochem 655:114872. https://doi.org/10.1016/j.ab.2022.114872