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Autophagy: a lysosomal degradation process for cellular homeostasis and its relationship with oral squamous cell carcinoma

  • Jung, Junyoung (Department of Nanopharmaceutical and Life Sciences, Graduate School, Kyung Hee University) ;
  • Kim, Joungmok (Department of Oral Biochemistry and Molecular Biology, Graduate School, Kyung Hee University) ;
  • Kim, Jeong Hee (Department of Nanopharmaceutical and Life Sciences, Graduate School, Kyung Hee University)
  • Received : 2021.06.10
  • Accepted : 2021.06.16
  • Published : 2021.06.30

Abstract

Autophagy is an evolutionarily well-conserved cellular homeostasis program that responds to various cellular stresses and degrades unnecessary or harmful intracellular materials in lysosomes. Accumulating evidence has shown that autophagy dysfunction often results in various human pathophysiological conditions, including metabolic disorders, cancers, and neurodegenerative diseases. The discovery of an autophagy machinery protein network has revealed underlying molecular mechanisms of autophagy, and advances in the understanding of its regulatory mechanism have provided novel therapeutic targets for treating human diseases. Recently, reports have emerged on the involvement of autophagy in oral squamous cell carcinoma (OSCC). Although the role of autophagy in cancer therapy is controversial, the beneficial use of the induction of autophagic cell death in OSCC has drawn significant attention. In this review, the types of autophagy, mechanism of autophagosome biogenesis, and modulating molecules and therapeutic candidates affecting the induction of autophagic cell death in OSCC are briefly described.

Keywords

References

  1. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science 2000;290:1717-21. doi: 10.1126/science.290.5497.1717.
  2. Yang Y, Klionsky DJ. Autophagy and disease: unanswered questions. Cell Death Differ 2020;27:858-71. doi: 10.1038/s41418-019-0480-9.
  3. Levine B, Kroemer G. Biological functions of autophagy genes: a disease perspective. Cell 2019;176:11-42. doi: 10.1016/j.cell.2018.09.048.
  4. Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med 2013;368:651-62. doi: 10.1056/NEJMra1205406.
  5. Li WW, Li J, Bao JK. Microautophagy: lesser-known self-eating. Cell Mol Life Sci 2012;69:1125-36. doi: 10.1007/s00018-011-0865-5.
  6. Catarino S, Pereira P, Girao H. Molecular control of chaperone-mediated autophagy. Essays Biochem 2017;61:663-74. doi: 10.1042/EBC20170057.
  7. Kaushik S, Cuervo AM. The coming of age of chaperonemediated autophagy. Nat Rev Mol Cell Biol 2018;19:365-81. doi: 10.1038/s41580-018-0001-6.
  8. Yoshii SR, Mizushima N. Monitoring and measuring autophagy. Int J Mol Sci 2017;18:1865. doi: 10.3390/ijms18091865.
  9. Chun Y, Kim J. Autophagy: an essential degradation program for cellular homeostasis and life. Cells 2018;7:278. doi: 10.3390/cells7120278.
  10. Zhao YG, Zhang H. Formation and maturation of autophagosomes in higher eukaryotes: a social network. Curr Opin Cell Biol 2018;53:29-36. doi: 10.1016/j.ceb.2018.04.003.
  11. Mercer TJ, Gubas A, Tooze SA. A molecular perspective of mammalian autophagosome biogenesis. J Biol Chem 2018;293:5386-95. doi: 10.1074/jbc.R117.810366.
  12. Hurley JH, Young LN. Mechanisms of autophagy initiation. Annu Rev Biochem 2017;86:225-44. doi: 10.1146/annurevbiochem-061516-044820.
  13. Suzuki K, Kubota Y, Sekito T, Ohsumi Y. Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 2007;12:209-18. doi: 10.1111/j.1365-2443.2007.01050.x.
  14. Zachari M, Ganley IG. The mammalian ULK1 complex and autophagy initiation. Essays Biochem 2017;61:585-96. doi: 10.1042/EBC20170021.
  15. Wolfson RL, Sabatini DM. The dawn of the age of amino acid sensors for the mTORC1 pathway. Cell Metab 2017;26:301-9. doi: 10.1016/j.cmet.2017.07.001.
  16. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017;168:960-76. doi: 10.1016/j.cell.2017.02.004.
  17. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-41. doi: 10.1038/ncb2152.
  18. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 2011;331:456-61. doi: 10.1126/science.1196371.
  19. Russell RC, Tian Y, Yuan H, Park HW, Chang YY, Kim J, Kim H, Neufeld TP, Dillin A, Guan KL. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol 2013;15:741-50. doi: 10.1038/ncb2757.
  20. Backer JM. The intricate regulation and complex functions of the Class III phosphoinositide 3-kinase Vps34. Biochem J 2016;473:2251-71. doi: 10.1042/BCJ20160170.
  21. Nascimbeni AC, Codogno P, Morel E. Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics. FEBS J 2017;284:1267-78. doi: 10.1111/febs.13987.
  22. Kihara A, Noda T, Ishihara N, Ohsumi Y. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol 2001;152:519-30. doi: 10.1083/jcb.152.3.519.
  23. Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell 2008;19:5360-72. doi: 10.1091/mbc.e08-01-0080.
  24. Kim YM, Jung CH, Seo M, Kim EK, Park JM, Bae SS, Kim DH. mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation. Mol Cell 2015;57:207-18. doi: 10.1016/j.molcel.2014.11.013.
  25. Munson MJ, Allen GF, Toth R, Campbell DG, Lucocq JM, Ganley IG. mTOR activates the VPS34-UVRAG complex to regulate autolysosomal tubulation and cell survival. EMBO J 2015;34:2272-90. doi: 10.15252/embj.201590992.
  26. Backer JM. The regulation and function of Class III PI3Ks: novel roles for Vps34. Biochem J 2008;410:1-17. doi: 10.1042/BJ20071427.
  27. Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol 2009;11:385-96. doi: 10.1038/ncb1846.
  28. Fan W, Nassiri A, Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc Natl Acad Sci U S A 2011;108:7769-74. doi: 10.1073/pnas.1016472108.
  29. Liang C, Lee JS, Inn KS, Gack MU, Li Q, Roberts EA, Vergne I, Deretic V, Feng P, Akazawa C, Jung JU. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol 2008;10:776-87. doi: 10.1038/ncb1740.
  30. Kim J, Kim YC, Fang C, Russell RC, Kim JH, Fan W, Liu R, Zhong Q, Guan KL. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell 2013;152:290-303. doi: 10.1016/j.cell.2012.12.016.
  31. Yuan HX, Russell RC, Guan KL. Regulation of PIK3C3/VPS34 complexes by MTOR in nutrient stress-induced autophagy. Autophagy 2013;9:1983-95. doi: 10.4161/auto.26058.
  32. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal 2014;20:460-73. doi: 10.1089/ars.2013.5371.
  33. Weidberg H, Shvets E, Elazar Z. Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem 2011;80:125-56. doi: 10.1146/annurev-biochem-052709-094552.
  34. Kim J, Dalton VM, Eggerton KP, Scott SV, Klionsky DJ. Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways. Mol Biol Cell 1999;10:1337-51. doi: 10.1091/mbc.10.5.1337.
  35. Ohsumi Y. Molecular dissection of autophagy: two ubiquitinlike systems. Nat Rev Mol Cell Biol 2001;2:211-6. doi: 10.1038/35056522.
  36. Shintani T, Mizushima N, Ogawa Y, Matsuura A, Noda T, Ohsumi Y. Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast. EMBO J 1999;18:5234-41. doi: 10.1093/emboj/18.19.5234.
  37. Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, Natsume T, Ohsumi Y, Yoshimori T. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J Cell Sci 2003;116(Pt 9):1679-88. doi: 10.1242/jcs.00381.
  38. Mizushima N, Yamamoto A, Hatano M, Kobayashi Y, Kabeya Y, Suzuki K, Tokuhisa T, Ohsumi Y, Yoshimori T. Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. J Cell Biol 2001;152:657-68. doi: 10.1083/jcb.152.4.657.
  39. Runwal G, Stamatakou E, Siddiqi FH, Puri C, Zhu Y, Rubinsztein DC. LC3-positive structures are prominent in autophagydeficient cells. Sci Rep 2019;9:10147. doi: 10.1038/s41598-019-46657-z.
  40. Bento CF, Renna M, Ghislat G, Puri C, Ashkenazi A, Vicinanza M, Menzies FM, Rubinsztein DC. Mammalian autophagy: how does it work? Annu Rev Biochem 2016;85:685-713. doi: 10.1146/annurev-biochem-060815-014556.
  41. Zhang Y, Mun SR, Linares JF, Ahn J, Towers CG, Ji CH, Fitzwalter BE, Holden MR, Mi W, Shi X, Moscat J, Thorburn A, Diaz-Meco MT, Kwon YT, Kutateladze TG. ZZ-dependent regulation of p62/SQSTM1 in autophagy. Nat Commun 2018;9:4373. doi: 10.1038/s41467-018-06878-8.
  42. Turco E, Witt M, Abert C, Bock-Bierbaum T, Su MY, Trapannone R, Sztacho M, Danieli A, Shi X, Zaffagnini G, Gamper A, Schuschnig M, Fracchiolla D, Bernklau D, Romanov J, Hartl M, Hurley JH, Daumke O, Martens S. FIP200 Claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. Mol Cell 2019;74:330-46.e11. doi: 10.1016/j.molcel.2019.01.035.
  43. Ravenhill BJ, Boyle KB, von Muhlinen N, Ellison CJ, Masson GR, Otten EG, Foeglein A, Williams R, Randow F. The cargo receptor NDP52 initiates selective autophagy by recruiting the ULK complex to cytosol-invading bacteria. Mol Cell 2019;74:320-9.e6. doi: 10.1016/j.molcel.2019.01.041.
  44. Vargas JNS, Wang C, Bunker E, Hao L, Maric D, Schiavo G, Randow F, Youle RJ. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol Cell 2019;74:347-62.e6. doi: 10.1016/j.molcel.2019.02.010.
  45. Zhou J, Peng X, Mei S. Autophagy in ovarian follicular development and atresia. Int J Biol Sci 2019;15:726-37. doi: 10.7150/ijbs.30369.
  46. Rivera C, Venegas B. Histological and molecular aspects of oral squamous cell carcinoma (Review). Oncol Lett 2014;8:7-11. doi: 10.3892/ol.2014.2103.
  47. Fujiwara T, Eguchi T, Sogawa C, Ono K, Murakami J, Ibaragi S, Asaumi JI, Calderwood SK, Okamoto K, Kozaki KI. Carci-nogenic epithelial-mesenchymal transition initiated by oral cancer exosomes is inhibited by anti-EGFR antibody cetuximab. Oral Oncol 2018;86:251-7. doi: 10.1016/j.oraloncology.2018.09.030.
  48. Li S, Zhang S, Chen J. c-Myc induced upregulation of long non-coding RNA SNHG16 enhances progression and carcinogenesis in oral squamous cell carcinoma. Cancer Gene Ther 2019;26:400-10. doi: 10.1038/s41417-018-0072-8.
  49. Petersen PE. Oral cancer prevention and control--the approach of the World Health Organization. Oral Oncol 2009;45:454-60. doi: 10.1016/j.oraloncology.2008.05.023.
  50. Alexandra T, Marina IM, Daniela M, Ioana SI, Maria B, Radu R, Maria TA, Tudor S, Maria G. Autophagy-a hidden but important actor on oral cancer scene. Int J Mol Sci 2020;21:9325.doi: 10.3390/ijms21239325.
  51. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008;451:1069-75. doi: 10.1038/nature06639.
  52. Meijer AJ. Autophagy research: lessons from metabolism. Autophagy 2009;5:3-5. doi: 10.4161/auto.5.1.7207.
  53. Yang Y, Chen D, Liu H, Yang K. Increased expression of lncRNA CASC9 promotes tumor progression by suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway in oral squamous cell carcinoma. Cell Death Dis 2019;10:41. doi: 10.1038/s41419-018-1280-8.
  54. Gao L, Wang Q, Ren W, Zheng J, Li S, Dou Z, Kong X, Liang X, Zhi K. The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma. Cell Death Dis 2020;11:488. doi: 10.1038/s41419-020-2693-8.
  55. Naik PP, Mukhopadhyay S, Praharaj PP, Bhol CS, Panigrahi DP, Mahapatra KK, Patra S, Saha S, Panda AK, Panda K, Paul S, Aich P, Patra SK, Bhutia SK. Secretory clusterin promotes oral cancer cell survival via inhibiting apoptosis by activation of autophagy in AMPK/mTOR/ULK1 dependent pathway. Life Sci 2021;264:118722. doi: 10.1016/j.lfs.2020.118722.
  56. Conrads TP, Tocci GM, Hood BL, Zhang CO, Guo L, Koch KR, Michejda CJ, Veenstra TD, Keay SK. CKAP4/p63 is a receptor for the frizzled-8 protein-related antiproliferative factor from interstitial cystitis patients. J Biol Chem 2006;281:37836-43. doi: 10.1074/jbc.M604581200.
  57. Wu YH, Wu WS, Lin LC, Liu CS, Ho SY, Wang BJ, Huang BM, Yeh YL, Chiu HW, Yang WL, Wang YJ. Bortezomib enhances radiosensitivity in oral cancer through inducing autophagy-mediated TRAF6 oncoprotein degradation. J Exp Clin Cancer Res 2018;37:91. doi: 10.1186/s13046-018-0760-0.
  58. Jhou AJ, Chang HC, Hung CC, Lin HC, Lee YC, Liu WT, Han KF, Lai YW, Lin MY, Lee CH. Chlorpromazine, an antipsychotic agent, induces G2/M phase arrest and apoptosis via regulation of the PI3K/AKT/mTOR-mediated autophagy pathways in human oral cancer. Biochem Pharmacol 2021;184:114403. doi: 10.1016/j.bcp.2020.114403.
  59. Sophia J, Kowshik J, Dwivedi A, Bhutia SK, Manavathi B, Mishra R, Nagini S. Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3β signalling pathway in oral cancer. Cell Death Dis 2018;9:1087. doi: 10.1038/s41419-018-1126-4.
  60. Lin CW, Chin HK, Lee SL, Chiu CF, Chung JG, Lin ZY, Wu CY, Liu YC, Hsiao YT, Feng CH, Bai LY, Weng JR. Ursolic acid induces apoptosis and autophagy in oral cancer cells. Environ Toxicol 2019;34:983-91. doi: 10.1002/tox.22769.
  61. Cheng MF, Lin SR, Tseng FJ, Huang YC, Tsai MJ, Fu YS, Weng CF. The autophagic inhibition oral squamous cell carcinoma cancer growth of 16-hydroxy-cleroda-3,14-dine-15,16-olide. Oncotarget 2017;8:78379-96. doi: 10.18632/oncotarget.18987.
  62. Thiyagarajan V, Sivalingam KS, Viswanadha VP, Weng CF. 16-hydroxy-cleroda-3,13-dien-16,15-olide induced glioma cell autophagy via ROS generation and activation of p38 MAPK and ERK-1/2. Environ Toxicol Pharmacol 2016;45:202-11. doi: 10.1016/j.etap.2016.06.005.
  63. Liu C, Lee WC, Huang BM, Chia YC, Chen YC, Chen YC. 16-Hydroxycleroda-3, 13-dien-15, 16-olide inhibits the proliferation and induces mitochondrial-dependent apoptosis through Akt, mTOR, and MEK-ERK pathways in human renal carcinoma cells. Phytomedicine 2017;36:95-107. doi: 10.1016/j.phymed.2017.09.021.
  64. Adhauliya N, Kalappanavar AN, Ali IM, Annigeri RG. Autophagy: a boon or bane in oral cancer. Oral Oncol 2016;61:120-6. doi: 10.1016/j.oraloncology.2016.09.001.
  65. Khan T, Relitti N, Brindisi M, Magnano S, Zisterer D, Gemma S, Butini S, Campiani G. Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas. Med Res Rev 2020;40:1002-60. doi: 10.1002/med.21646.