Ukr.Biochem.J. 2020; Volume 92, Issue 4, Jul-Aug, pp. 24-34

doi: https://doi.org/10.15407/ubj92.04.024

Adaptor protein Ruk/CIN85 affects redox balance in breast cancer cells

I. R. Horak*, N. V. Latyshko, O. O. Hudkova, T. O. Kishko,
O. V. Khudiakova, D. S. Gerashchenko, T. D. Skaterna,
I. P. Krysiuk, S. G. Shandrenko, L. B. Drobot

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: iryna.horak@gmail.com

Received: 25 February 2020; Accepted: 15 May 2020

Excessive reactive oxygen species (ROS) production may lead to damage of cellular proteins, lipids and DNA, and cause cell death. Our previous findings demonstrated that increased level of adaptor protein Ruk/CIN85 contributes to breast cancer cells malignancy. The aim of this study was to investigate the role of Ruk/CIN85 in the maintaining of the redox balance in cancer cells. Mouse breast adenocarcinoma 4T1 cells with different levels of Ruk/CIN85 expression were used as a model in this study. Activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), aldehyde dehydrogenase (ALDH) and formaldehyde dehydrogenase (FALDH), as well as H2O2 and aldehydes content were measured using fluorometric assays. Gene expression correlations between Ruk/CIN85 and antioxidant enzymes in breast cancer samples were analyzed using ist.medisapiens transcriptomic database. It was demonstrated that Ruk/CIN85-overexpressing 4T1 cells were characterized by increased production of H2O2 and reduced activities of CAT, GPx and SOD. Overexpression of Ruk/CIN85 resulted in decreased content of aldehydes together with increased activity of ALDH, while in Ruk/CIN85-knocked down 4T1 cells, activities of ALDH and FALDH were decreased. The data of transcriptomic analysis revealed the correlations between SH3KBP1 expression and CAT, GPX4, ALDH1A1, ALDH1L1, ALDH2, GSR, SOD1 in human breast carcinomas samples. The obtained results indicate that adaptor protein Ruk/CIN85 affects redox balance in mouse breast adenocarcinoma 4T1 cells.

Keywords: , , , ,


References:

  1. Poyton RP, Ball KA, Castello PR. Mitochondrial Generation of Free Radicals and Hypoxic Signaling. Trends Endocrinol Metab. 2009;20(7):332-40. PubMed, CrossRef
  2. Schieber M, Chandel NS. ROS Function in Redox Signaling and Oxidative Stress. Curr Biol. 2014;24(10):R453-62. PubMed, PubMedCentral, CrossRef
  3. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative Stress, Inflammation, and Cancer: How Are They Linked? Free Radic Biol Med. 2010;49(11):1603-16. PubMed, PubMedCentral, CrossRef
  4. Glorieux C, Calderon PB. Catalase, a Remarkable Enzyme: Targeting the Oldest Antioxidant Enzyme to Find a New Cancer Treatment Approach. Biol Chem. 2017;398(10):1095-1108. PubMed, CrossRef
  5. Ma-On C, Sanpavat A, Whongsiri P, Suwannasin S, Hirankarn N, Tangkijvanich PT, Boonla C. Oxidative Stress Indicated by Elevated Expression of Nrf2 and 8-OHdG Promotes Hepatocellular Carcinoma Progression. Med Oncol. 2017;34(4):57. PubMed, CrossRef
  6. Pereira EJ, Smolko CM, Janes KA. Computational Models of Reactive Oxygen Species as Metabolic Byproducts and Signal-Transduction Modulators. Front Pharmacol. 2016;7:457. PubMed, PubMedCentral, CrossRef
  7. Luo M, Shang L, Brooks MD, Eiagge E, Zhu Y, Buschhaus JM, Conley S, Fath MA, Davis A, Gheordunescu E, Wang Y, Harouaka R, Lozier A, Triner D, McDermott S, Merajver SD, Luker GD, Spitz DR, Wicha MS. Targeting Breast Cancer Stem Cell State Equilibrium Through Modulation of Redox Signaling. Cell Metab. 2018;28(1):69-86.e6. PubMed, PubMedCentral, CrossRef
  8. Pawson T. Dynamic Control of Signaling by Modular Adaptor Proteins. Curr Opin Cell Biol. 2007;19(2):112-116. PubMed, CrossRef
  9. Good MC, Zalatan JG, Lim WA. Scaffold Proteins: Hubs for Controlling the Flow of Cellular Information. Science. 2011;332(6030):680-686.  PubMed, PubMedCentral, CrossRef
  10. Havrylov S, Redowicz MJ, Buchman VL. Emerging Roles of Ruk/CIN85 in Vesicle-Mediated Transport, Adhesion, Migration and Malignancy. Traffic. 2010;11(6):721-731. PubMed, CrossRef
  11. Ma Y, Ye F, Xie X, Zhou C, Lu W. Significance of PTPRZ1 and CIN85 Expression in Cervical Carcinoma. Arch Gynecol Obstet. 2011;284(3):699-704.
    PubMed, CrossRef
  12. Cascio S, Finn OJ. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis. Cancers (Basel). 2015;7(1):342-352. PubMed, PubMedCentral, CrossRef
  13. Horak IR, Pasichnyk GV, Gerashchenko DS, Knopfova L, Borsig L, Drobot LB. Adaptor protein Ruk/CIN85 modulates manifestation of cancer stem cells (CSCs) features in mouse breast adenocarcinoma 4T1 cells. Rep Nat Acad Sci Ukraine. 2018;(12):101-109. CrossRef
  14. Hirakawa K. Fluorometry of Hydrogen Peroxide Using Oxidative Decomposition of Folic Acid. Anal Bioanal Chem. 2006;386(2):244-248. PubMed, CrossRef
  15. Aisaka K, Uwajima T, Terada O. Purification and Properties of Glutathione Peroxidase from Mucor hiemalis. Agric Biol Chem. 1983;47(5):1107-1113. CrossRef
  16. Koivula T, Koivusalo M, Lindros KO. Liver Aldehyde and Alcohol Dehydrogenase Activities in Rat Strains Genetically Selected for Their Ethanol Preference. Biochem Pharmacol. 1975;24(19):1807-1811. PubMed, CrossRef
  17. Tran S, Nowicki M, Chatterjee D, Gerlai R. Acute and Chronic Ethanol Exposure Differentially Alters Alcohol Dehydrogenase and Aldehyde Dehydrogenase Activity in the Zebrafish Liver. Prog Neuropsychopharmacol Biol Psychiatry. 2015;56:221-226. PubMed, CrossRef
  18. Nash T. The Colorimetric Estimation of Formaldehyde by Means of the Hantzsch Reaction. Biochem J. 1953;55(3):416-421. PubMed, PubMedCentral, CrossRef
  19. Bradford MM. A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal Biochem. 1976;72(1-2):248-254. PubMed, CrossRef
  20. Ergin V, Hariry RE, Karasu C. Carbonyl Stress in Aging Process: Role of Vitamins and Phytochemicals as Redox Regulators. Aging Dis. 2013;4(5):276-294. PubMed, PubMedCentral, CrossRef
  21. Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R. Advanced Lipid Peroxidation End Products in Oxidative Damage to Proteins. Potential Role in Diseases and Therapeutic Prospects for the Inhibitors. Br J Pharmacol. 2008;153(1):6-20. PubMed, PubMedCentral, CrossRef
  22. Barroso-Sousa R, Metzger-Filho O. Differences Between Invasive Lobular and Invasive Ductal Carcinoma of the Breast: Results and Therapeutic Implications. Ther Adv Med Oncol. 2016;8(4):261-266.  PubMed, PubMedCentral, CrossRef
  23. McCart Reed AE, Kutasovic JR, Lakhani SR, Simpson PT. Invasive Lobular Carcinoma of the Breast: Morphology, Biomarkers and ‘Omics. Breast Cancer Res. 2015;17(1):12. PubMed, PubMedCentral, CrossRef
  24. Bazalii AV, Horak IR, Pasichnyk GV, Komisarenko SV, Drobot LB. Transcriptional regulation of NOX genes express ion in human breast adenocarcinoma MCF-7 cells is modulated by adaptor protein Ruk/CIN85. Ukr Biochem J. 2016; 88(1): 119-25. PubMed, CrossRef
  25. Bazalii AV, Samoylenko AA, Petukhov DM, Rynditch AV, Redowicz M-J, Drobot LB. Interaction between adaptor proteins Ruk/CIN85 and Tks4 in normal and tumor cells of different tissue origins. Biopolym Cell. 2014;30(1):37-41.  CrossRef
  26. Rhee SG. Cell Signaling. H2O2, a Necessary Evil for Cell Signaling. Science. 2006;312(5782):1882-1883. PubMed, CrossRef
  27. Finkel T. From Sulfenylation to Sulfhydration: What a Thiolate Needs to Tolerate. Sci Signal. 2012;5(215):pe10. PubMed, CrossRef
  28. Samoylenko A, Vynnytska-Myronovska B, Byts N, Kozlova N, Basaraba O, Pasichnyk G, Palyvoda K, Bobak Ya, Barska M, Mayevska O, Rzhepetsky Yu, Shuvayeva H, Lyzogubov V, Usenko V, Savran V, Volodko N, Buchman V, Kietzmann T, Drobot L. Increased Levels of the HER1 Adaptor Protein Rukl/CIN85 Contribute to Breast Cancer Malignancy. Carcinogenesis. 2012;33(10):1976-84. PubMed, CrossRef
  29. Hoxhaj G, Manning BD. The PI3K-AKT Network at the Interface of Oncogenic Signalling and Cancer Metabolism. Nat Rev Cancer. 2020;20(2):74-88. PubMed, PubMedCentral, CrossRef
  30. Kumari S, Badana AK, G MM, G S, Malla RR. Reactive Oxygen Species: A Key Constituent in Cancer Survival. Biomark Insights. 2018;13:1177271918755391. PubMed, PubMedCentral, CrossRef
  31. Görlach A, Kietzmann T. Superoxide and Derived Reactive Oxygen Species in the Regulation of Hypoxia-Inducible Factors. Methods Enzymol. 2007;435:421-446.  PubMed, CrossRef
  32. Simon AR, Rai U, Fanburg BL, Cochran BH. Activation of the JAK-STAT Pathway by Reactive Oxygen Species. Am J Physiol. 1998;275(6):C1640-C1652. PubMed, CrossRef
  33. Liu  B, Chen Y,  Clair Dk. ROS and p53: A Versatile Partnership. Free Radic Biol Med. 2008;44(8):1529-35. PubMed, PubMedCentral, CrossRef
  34. Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. 1995;270(5234):296-299. PubMed, CrossRef
  35. Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG. Epidermal Growth Factor (EGF)-induced Generation of Hydrogen Peroxide. Role in EGF Receptor-Mediated Tyrosine Phosphorylation. J Biol Chem. 1997;272(1):217-221. PubMed
  36. Meng TC, Fukada T, Tonks NK. Reversible Oxidation and Inactivation of Protein Tyrosine Phosphatases in Vivo. Mol Cell. 2002;9(2):387-399. PubMed, CrossRef
  37. Moreb JS. Aldehyde Dehydrogenase as a Marker for Stem Cells. Curr Stem Cell Res Ther. 2008;3(4):237-246. PubMed, CrossRef
  38. Luo M, Brooks M, Wicha MS. Epithelial-mesenchymal Plasticity of Breast Cancer Stem Cells: Implications for Metastasis and Therapeutic Resistance. Curr Pharm Des. 2015;21(10):1301-1310. PubMed, PubMedCentral, CrossRef
  39. Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, Tamaki Y, Noguchi S. Association of Breast Cancer Stem Cells Identified by Aldehyde Dehydrogenase 1 Expression With Resistance to Sequential Paclitaxel and Epirubicin-Based Chemotherapy for Breast Cancers. Clin Cancer Res. 2009;15(12):4234-4241. PubMed, CrossRef
  40. Wang Y, Li W, Patel SS, Cong J, Zhang N, Sabbatino F, Liu X, Qi Y, Huang P, Lee H, Taghian A, Li JJ, DeLeo AB, Ferrone S, Epperly MW, Ferrone CR, Ly A, Brachtel EF, Wang X. Blocking the formation of radiation–induced breast cancer stem cells. Oncotarget. 2014; 5 (11): 3743–3755.
  41. Vassalli G. Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells. Stem Cells Int. 2019;2019:3904645. PubMed, PubMedCentral, CrossRef
  42. Leone A, Roca MS, Ciardiello C, Costantini S, Budillon A. Oxidative Stress Gene Expression Profile Correlates With Cancer Patient Poor Prognosis: Identification of Crucial Pathways Might Select Novel Therapeutic Approaches. Oxid Med Cell Longev. 2017;2017:2597581. PubMed, PubMedCentral, CrossRef
  43. Singh S, Brocker C, Koppaka V, Chen Y, Jackson BC, Matsumoto A, Thompson DC, Vasiliou V. Aldehyde Dehydrogenases in Cellular Responses to oxidative/electrophilic Stress. Free Radic Biol Med. 2013;56:89-101. PubMed, PubMedCentral, CrossRef
  44. Kang MY, Kim HB, Piao C, Lee KH, Hyun JW, Chang IY, You HJ. The Critical Role of Catalase in Prooxidant and Antioxidant Function of p53. Cell Death Differ. 2013;20(1):117-129. PubMed, PubMedCentral, CrossRef
  45. Glorieux С, Dejeans N, Sid B, Beck R, Calderon PB, Verrax J. Catalase Overexpression in Mammary Cancer Cells Leads to a Less Aggressive Phenotype and an Altered Response to Chemotherapy. Biochem Pharmacol. 2011;82(10):1384-1390. PubMed, CrossRef
  46. Wang Y, Branicky R, Noë A, Hekimi S. Superoxide Dismutases: Dual Roles in Controlling ROS Damage and Regulating ROS Signaling. J Cell Biol. 2018;217(6):1915-1928. PubMed, PubMedCentral, CrossRef

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