نوع مقاله : مقاله مروری

نویسندگان

1 دکترای بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران

2 دانشجوی دکترا بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران

3 دانشجوی فوق لیسانس بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی شیراز، شیراز، ایران

چکیده

تداخل در عملکرد طبیعی شبکه آندوپلاسمی تحت شرایط استرس منجر به راه اندازی مسیر کاملاً حفاظت شده ای تحت نام پاسخ استرس سلولی  یا پاسخ پروتئینهای تا نخورده (UPR; Unfolded protein response) می گردد که هدف اولیه این مسیر جبران اختلالات ایجاد شده یا بازگرداندن شرایط نرمال سلولی است و درصورت طولانی و شدید بودن استرس شبکه آندوپلاسمی حتی قادر به راه اندازی مسیر مرگ سلولی (Apoptosis) نیز می باشد. مسیر پاسخ به استرس پروتئین های بد تا شده دارای سه بازوی اصلی است که هریک پس از فعال شدن منجر به اثرات متفاوتی بر تغییر بیان ژنهای ضروری درون سلول می شوند. در سالهای اخیر مولکولهای تنظیم کننده پاسخ استرس شبکه آندوپلاسمی بعنوان گزینه های  بسیار قوی و موثر برای اهداف دارویی و درمانی در بسیاری از بیماری ها از جمله : سرطان، آلزایمر، پارکینسون، دیابت، بیماری های قلبی و کبدی و آلرژی مورد توجه محققین قرار گرفته اند.

کلیدواژه‌ها

عنوان مقاله [English]

Evaluation of Endoplasmic Reticulum Stress Mechanism and Unfold Protein Response Signaling in Cancer

نویسندگان [English]

  • Pouneh Mokaram 1
  • Sanaz Dastghaib 2
  • Morvarid Siri 3
  • Sedigheh Rezayi 3

1 PhD of clinical biochemistry, Department of biochemistry, Shiraz University of medical sciences, Shiraz, Iran

2 PhD candidate in clinical biochemistry, Department of biochemistry, Shiraz University of medical sciences, Shiraz, Iran

3 Master of clinical biochemistry, Department of biochemistry, Shiraz University of medical sciences, Shiraz, Iran

چکیده [English]

Perturbation of endoplasmic reticulum (ER) homeostasis under a stressful situation leads to a stress condition termed “ER stress” which induces the activation of a finely regulated program defined as unfolded protein response (UPR), whose primary aim is to restore disorders or normal cell conditions. Under prolonged or sustained ER, stress conditions may result in activation-induced cell death. The UPR has three main arms; activation of each arm can lead to various effects on the expression of essential genes in cells.
In recent years, ER stress response regulator molecules have been considered by the researchers as a very strong and effective candidate for pharmaceutical and therapeutic purposes in many diseases, including cancer, Alzheimer's disease, Parkinson's disease, diabetes, heart and liver diseases, and allergies.

کلیدواژه‌ها [English]

  • Endoplasmic reticulum
  • Stress
  • Cancer
  • UPR
  • Protein Folding
  • Cell death mechanisms
  1. Ozgur R, Uzilday B, Iwata Y, Koizumi N, Turkan I. Interplay between unfolded protein response and reactive oxygen species: a dynamic duo. Journal of experimental botany. 2018:ery040.
  2. Manalo RVM, Medina PMB. The endoplasmic reticulum stress response in disease pathogenesis and pathophysiology. Egyptian Journal of Medical Human Genetics. 2017.
  3. Schröder M. Endoplasmic reticulum stress responses. Cellular and molecular life sciences. 2008;65(6):862-94.
  4. Kapoor A, Sanyal AJ. Endoplasmic reticulum stress and the unfolded protein response. Clinics in liver disease. 2009;13(4):581-90.
  5. Salminen A, Kaarniranta K. ER stress and hormetic regulation of the aging process. Ageing research reviews. 2010;9(3):211-7.
  6. Kim I, Xu W, Reed JC. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nature reviews Drug discovery. 2008;7(12):1013.
  7. Kim SR, Lee YC. Endoplasmic reticulum stress and the related signaling networks in severe asthma. Allergy, asthma & immunology research. 2015;7(2):106-17.
  8. Kelsen SG. The unfolded protein response in chronic obstructive pulmonary disease. Annals of the American Thoracic Society. 2016;13(Supplement 2):S138-S45.
  9. Wang M, Wey S, Zhang Y, Ye R, Lee AS. Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders. Antioxidants & redox signaling. 2009;11(9):2307-16.
  10. Regulation H. The Unfolded Protein Response: From Stress Pathway to. science. 2011;1209038(1081):334.
  11. Lindholm D, Korhonen L, Eriksson O, Kõks S. Recent insights into the role of unfolded protein response in ER stress in health and disease. Frontiers in cell and developmental biology. 2017;5:48.
  12. Senft D, Ze’ev AR. UPR, autophagy, and mitochondria crosstalk underlies the ER stress response. Trends in biochemical sciences. 2015;40(3):141-8.
  13. Cybulsky AV. Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases. Nature Reviews Nephrology. 2017;13(11):681.
  14. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nature reviews Molecular cell biology. 2007;8(7):519.
  15. Doultsinos D, Avril T, Lhomond S, Dejeans N, Guedat P, Chevet E. Control of the unfolded protein response in health and disease. SLAS DISCOVERY: Advancing Life Sciences R&D. 2017;22(7):787-800.
  16. Gopal U, Pizzo SV. The Endoplasmic Reticulum Chaperone GRP78 Also Functions as a Cell Surface Signaling Receptor. Cell Surface GRP78, a New Paradigm in Signal Transduction Biology: Elsevier; 2018. p. 9-40.
  17. Corazzari M, Gagliardi M, Fimia GM, Piacentini M. Endoplasmic reticulum stress, unfolded protein response, and cancer cell fate. Frontiers in oncology. 2017;7:78.
  18. Chevet E, Hetz C, Samali A. Endoplasmic reticulum stress–activated cell reprogramming in oncogenesis. Cancer discovery. 2015;5(6):586-97.
  19. Raven JF, Baltzis D, Wang S, Mounir Z, Papadakis AI, Gao HQ, et al. PKR and PKR-like endoplasmic reticulum kinase induce the proteasome-dependent degradation of cyclin D1 via a mechanism requiring eukaryotic initiation factor 2α phosphorylation. Journal of Biological Chemistry. 2008;283(6):3097-108.
  20. Molina-Ruiz FJ, Gonzalez R, Rodriguez-Hernandez MA, Navarro-Villaran E, Padillo FJ, Muntane J. Antitumoral activity of Sorafenib in hepatocellular Carcinoma: effects on cell survival and death pathways, cell metabolism reprogramming, and on nitrosative and oxidative str. Critical Reviews™ in Oncogenesis.
  21. McQuiston A, Diehl JA. Recent insights into PERK-dependent signaling from the stressed endoplasmic reticulum. F1000Research. 2017;6.
  22. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, et al. IRE1 signaling affects cell fate during the unfolded protein response. science. 2007;318(5852):944-9.
  23. Lin JH, Li H, Zhang Y, Ron D, Walter P. Divergent effects of PERK and IRE1 signaling on cell viability. PloS one. 2009;4(1):e4170.
  24. Rahmati M, Amanpour S, Kharman-Biz A, Moosavi MA. Endoplasmic Reticulum Stress as a Therapeutic Target in Cancer: A mini review. Basic & Clinical Cancer Research. 2017;9(2):38-48.
  25. Drogat B, Auguste P, Nguyen DT, Bouchecareilh M, Pineau R, Nalbantoglu J, et al. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo. Cancer research. 2007;67(14):6700-7.
  26. Maurel M, Chevet E, Tavernier J, Gerlo S. Getting RIDD of RNA: IRE1 in cell fate regulation. Trends in biochemical sciences. 2014;39(5):245-54.
  27. Agostinis P, Afshin S. Endoplasmic reticulum stress in health and disease: Springer Science & Business Media; 2012.
  28. Nadanaka S, Okada T, Yoshida H, Mori K. Role of disulfide bridges formed in the luminal domain of ATF6 in sensing endoplasmic reticulum stress. Molecular and cellular biology. 2007;27(3):1027-43.
  29. Yuan K, He H-H, Zhang C-Z, Li X-Y, Weng S-P, He J-G, et al. Litopenaeus vannamei activating transcription factor 6 alpha gene involvement in ER-stress response and white spot symptom virus infection. Fish & shellfish immunology. 2017;70:129-39.
  30. Forouhan M, Mori K, Boot-Handford R. Paradoxical roles of ATF6α and ATF6β in modulating disease severity caused by mutations in collagen X. Matrix Biology. 2018.
  31. Li X, Zhang K, Li Z. Unfolded protein response in cancer: the physician's perspective. Journal of hematology & oncology. 2011;4(1):8.
  32. Yorimitsu T, Nair U, Yang Z, Klionsky DJ. ER stress triggers autophagy. Journal of Biological Chemistry. 2006.
  33. Gaist D, Andersen L, Hallas J, Sørensen HT, Schrøder H, Friis S. Use of statins and risk of glioma: a nationwide case–control study in Denmark. British journal of cancer. 2013;108(3):715.
  34. Yan Y, Xu Z, Dai S, Qian L, Sun L, Gong Z. Targeting autophagy to sensitive glioma to temozolomide treatment. Journal of experimental & clinical cancer research. 2016;35(1):23.
  35. Clarke R, Cook KL, Hu R, Facey CO, Tavassoly I, Schwartz JL, et al. Endoplasmic reticulum stress, the unfolded protein response, autophagy, and the integrated regulation of breast cancer cell fate. Cancer research. 2012;72(6):1321-31.
  36. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nature cell biology. 2000;2(6):326.
  37. Verfaillie T, Garg AD, Agostinis P. Targeting ER stress induced apoptosis and inflammation in cancer. Cancer letters. 2013;332(2):249-64.
  38. Oakes SA, Papa FR. The role of endoplasmic reticulum stress in human pathology. Annual Review of Pathology: Mechanisms of Disease. 2015;10:173-94.
  39. Wang Y, Wang JH, Zhang XL, Wang XL, Yang L. Endoplasmic reticulum chaperone glucose-regulated protein 78 in gastric cancer: An emerging biomarker. Oncology Letters.
  40. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. science. 2011;334(6059):1081-6.
  41. Corazzari M, Rapino F, Ciccosanti F, Giglio P, Antonioli M, Conti B, et al. Oncogenic BRAF induces chronic ER stress condition resulting in increased basal autophagy and apoptotic resistance of cutaneous melanoma. Cell death and differentiation. 2015;22(6):946.
  42. Hill DS, Lovat PE, Haass NK. Induction of endoplasmic reticulum stress as a strategy for melanoma therapy: is there a future? Melanoma Management. 2014;1(2):127-37.
  43. Gottesman MM. Mechanisms of cancer drug resistance. Annual review of medicine. 2002;53(1):615-27.
  44. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nature Reviews Cancer. 2013;13(10):714.
  45. Longley D, Johnston P. Molecular mechanisms of drug resistance. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland. 2005;205(2):275-92.
  46. Fu Y, Li J, Lee AS. GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation–induced apoptosis. Cancer research. 2007;67(8):3734-40.
  47. Hu R, Warri A, Jin L, Zwart A, Riggins RB, Clarke R. NFκB Signaling is required for XBP1 (U and S) Mediated Effects on Antiestrogen Responsiveness and Cell Fate Decisions in Breast Cancer. Molecular and cellular biology. 2014:MCB. 00847-14.
  48. Yeung B, Kwan B, He Q, Lee A, Liu J, Wong A. Glucose-regulated protein 78 as a novel effector of BRCA1 for inhibiting stress-induced apoptosis. Oncogene. 2008;27(53):6782.
  49. Fujimoto A, Kawana K, Taguchi A, Adachi K, Sato M, Nakamura H, et al. Inhibition of endoplasmic reticulum (ER) stress sensors sensitizes cancer stem-like cells to ER stress-mediated apoptosis. Oncotarget. 2016;7(32):51854.
  50. Ranganathan AC, Adam AP, Zhang L, Aguirre-Ghiso JA. Tumor cell dormancy induced by p38SAPK and ER-stress signaling: an adaptive advantage for metastatic cells? Cancer biology & therapy. 2006;5(7):729-35.
  51. Pi L, Li X, Song Q, Shen Y, Lu X, Di B. Knockdown of glucose‑regulated protein 78 abrogates chemoresistance of hypopharyngeal carcinoma cells to cisplatin induced by unfolded protein in response to severe hypoxia. Oncology Letters. 2014;7(3):685-92.
  52. Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer research. 2007;67(8):3496-9.
  53. Visioli F, Wang Y, Alam GN, Ning Y, Rados PV, Nör JE, et al. Glucose-regulated protein 78 (Grp78) confers chemoresistance to tumor endothelial cells under acidic stress. PloS one. 2014;9(6):e101053.
  54. Pyrko P, Schönthal AH, Hofman FM, Chen TC, Lee AS. The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. Cancer research. 2007;67(20):9809-16.
  55. Piton N, Wason J, Colasse É, Cornic M, Lemoine F, Le Pessot F, et al. Endoplasmic reticulum stress, unfolded protein response and development of colon adenocarcinoma. Virchows Archiv. 2016;469(2):145-54.
  56. Salazar M, Hernandez-Tiedra S, Torres S, Lorente M, Guzman M, Velasco G. Detecting autophagy in response to ER stress signals in cancer. Methods in enzymology: Elsevier; 2011. p. 297-317.
  57. Hetz C, Saxena S. ER stress and the unfolded protein response in neurodegeneration. Nature Reviews Neurology. 2017;13(8):477.