Skip to main content
SpringerLink
Log in

Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights

  • Review Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

According to the findings of recent research, Helicobacter Pylori (H. pylori) infection is not only the primary cause of gastric cancer (GC), but it is also linked to the spread and invasion of GC through a number of processes and factors that contribute to virulence. In this study, we discussed that H. pylori infection can increase autophagy in GC tumor cells, leading to poor prognosis in such patients. Until now, the main concerns have been focused on H. pylori’s role in GC development. According to our hypothesis, however, H. pylori infection may also lead to GC dormancy, metastasis, and recurrence by stimulating autophagy. Therefore, understanding how H. pylori possess these processes through its virulence factors and various microRNAs can open new windows for providing new prevention and/or therapeutic approaches to combat GC dormancy, metastasis, and recurrence which can occur in GC patients with H. pylori infection with targeting autophagy and eradicating H. pylori infection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and materials

Not applicable.

Abbreviations

miRNA:

MicroRNA

AMPK:

AMP-activated protein kinase

mTORC1:

Mammalian target of rapamycin complex 1

AKT:

Protein kinase B (PKB)

PI3K:

Phosphatidylinositol 3-kinases

VPS34:

Vacuolar protein sorting-associated protein 34

Atg6:

Autophagy-related gene 6

References

  1. Zhang L, Zou L, Sun P. Relationship between miR-378c and YY1 expression in patients with gastric cancer and the clinicopathological features. Cell Mol Biol Lett. 2021;26(1):1–10.

    Google Scholar 

  2. Karami Fath M, Babakhaniyan K, Zokaei M, Yaghoubian A, Akbari S, Khorsandi M, et al. Anti-cancer peptide-based therapeutic strategies in solid tumors. Cell Mol Biol Lett. 2022;27(1):33.

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Zalpoor H, Nabi-Afjadi M, Forghaniesfidvajani R, Tavakol C, Farahighasreaboonasr F, Pakizeh F, et al. Quercetin as a JAK–STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases. Cell Mol Biol Lett. 2022;27(1):60.

    PubMed  PubMed Central  CAS  Google Scholar 

  4. Eyvazi S, Khamaneh AM, Tarhriz V, Bandehpour M, Hejazi MS, Sadat ATE, et al. CpG islands methylation analysis of CDH11, EphA5, and HS3ST2 genes in gastric adenocarcinoma patients. J Gastrointest Cancer. 2020;51(2):579–83.

    PubMed  CAS  Google Scholar 

  5. Kanaji S, Suzuki S, Matsuda Y, Hasegawa H, Yamamoto M, Yamashita K, et al. Recent updates in perioperative chemotherapy and recurrence pattern of gastric cancer. Ann Gastroenterol Surg. 2018;2(6):400–5.

    PubMed  PubMed Central  Google Scholar 

  6. Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, Pignon J-P, et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 2010;303(17):1729–37.

    PubMed  CAS  Google Scholar 

  7. Kanda M, Kodera Y, Sakamoto J. Updated evidence on adjuvant treatments for gastric cancer. Expert Rev Gastroenterol Hepatol. 2015;9(12):1549–60.

    PubMed  CAS  Google Scholar 

  8. Karrison TG, Ferguson DJ, Meier P. Dormancy of mammary carcinoma after mastectomy. J Natl Cancer Inst. 1999;91(1):80–5.

    PubMed  CAS  Google Scholar 

  9. McGowan PM, Kirstein JM, Chambers AF. Micrometastatic disease and metastatic outgrowth: clinical issues and experimental approaches. Future Oncol. 2009;5(7):1083–98.

    PubMed  CAS  Google Scholar 

  10. Mowers EE, Sharifi MN, Macleod KF. Autophagy in cancer metastasis. Oncogene. 2017;36(12):1619–30.

    PubMed  CAS  Google Scholar 

  11. Sosa MS, Bragado P, Aguirre-Ghiso JA. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer. 2014;14(9):611–22.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Lu Z, Luo RZ, Lu Y, Zhang X, Yu Q, Khare S, et al. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J Clin Investig. 2008;118(12):3917–29.

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Khaledi M, Bagheri N, Validi M, Zamanzad B, Afkhami H, Fathi J, et al. Determination of CagA EPIYA motif in Helicobacter pylori strains isolated from patients with digestive disorder. Heliyon. 2020;6(9):e04971.

    PubMed  PubMed Central  CAS  Google Scholar 

  14. Bernegger S, Vidmar R, Fonovic M, Posselt G, Turk B, Wessler S. Identification of desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells. Cell Commun Signal. 2021;19(1):1–12.

    Google Scholar 

  15. Eyvazi S, Vostakolaei MA, Dilmaghani A, Borumandi O, Hejazi MS, Kahroba H, et al. The oncogenic roles of bacterial infections in development of cancer. Microb Pathog. 2020;141:104019.

    PubMed  CAS  Google Scholar 

  16. Hooi JK, Lai WY, Ng WK, Suen MM, Underwood FE, Tanyingoh D, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology. 2017;153(2):420–9.

    PubMed  Google Scholar 

  17. Polk DB, Peek RM. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010;10(6):403–14.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Investig. 2009;119(6):1420–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Bessede E, Staedel C, Amador LA, Nguyen P, Chambonnier L, Hatakeyama M, et al. Helicobacter pylori generates cells with cancer stem cell properties via epithelial–mesenchymal transition-like changes. Oncogene. 2014;33(32):4123–31.

    PubMed  CAS  Google Scholar 

  20. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.

    PubMed  CAS  Google Scholar 

  21. Courtois S, Haykal M, Bodineau C, Sifré E, Azzi-Martin L, Ménard A, et al. Autophagy induced by Helicobacter pylori infection is necessary for gastric cancer stem cell emergence. Gastric Cancer. 2021;24(1):133–44.

    PubMed  CAS  Google Scholar 

  22. Azargun R, Gholizadeh P, Sadeghi V, Hosainzadegan H, Tarhriz V, Memar MY, et al. Molecular mechanisms associated with quinolone resistance in Enterobacteriaceae: review and update. Trans R Soc Trop Med Hyg. 2020;114(10):770–81.

    PubMed  CAS  Google Scholar 

  23. Eslami M, Yousefi B, Kokhaei P, Arabkari V, Ghasemian A. Current information on the association of Helicobacter pylori with autophagy and gastric cancer. J Cell Physiol. 2019;234(9):14800–11.

    PubMed  CAS  Google Scholar 

  24. Yang Y, Shu X, Xie C. An overview of autophagy in Helicobacter pylori infection and related gastric cancer. Front Cell Infect Microbiol. 2022;12:410.

    Google Scholar 

  25. Norouzi A, Davodabadi F, Varnosfaderani SMN, Zalpoor H. The potential role of acid ceramidase in oral squamous cell carcinoma chemo-resistance by inducing autophagy. Hum Cell. 2023;36:2273–5.

    PubMed  CAS  Google Scholar 

  26. Zalpoor H, Akbari A, Nayerain Jazi N, Liaghat M, Bakhtiyari M. Possible role of autophagy induced by COVID-19 in cancer progression, chemo-resistance, and tumor recurrence. Infect Agents Cancer. 2022;17(1):38.

    CAS  Google Scholar 

  27. Zhang L, Hu W, Cho CH, Chan FK, Yu J, Fitzgerald JR, et al. Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori. J Pathol. 2018;244(4):432–44.

    PubMed  CAS  Google Scholar 

  28. Zalpoor H, Bakhtiyari M, Akbari A, Aziziyan F, Shapourian H, Liaghat M, et al. Potential role of autophagy induced by FLT3-ITD and acid ceramidase in acute myeloid leukemia chemo-resistance: new insights. Cell Commun Signal. 2022;20(1):172.

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Zalpoor H, Rezaei M, Yahyazadeh S, Ganjalikhani-Hakemi M. Flt3-ITD mutated acute myeloid leukemia patients and COVID-19: potential roles of autophagy and HIF-1α in leukemia progression and mortality. Hum Cell. 2022;35(4):1304–5.

    PubMed Central  CAS  Google Scholar 

  30. Mostafavi S, Zalpoor H, Hassan ZM. The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors. Cell Mol Biol Lett. 2022;27(1):1–24.

    Google Scholar 

  31. Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7(11):629–41.

    PubMed  PubMed Central  CAS  Google Scholar 

  32. Isomoto H, Moss J, Hirayama T. Pleiotropic actions of Helicobacter pylori vacuolating cytotoxin, VacA. Tohoku J Exp Med. 2010;220(1):3–14.

    PubMed  CAS  Google Scholar 

  33. Willhite DC, Cover TL, Blanke SR. Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation. J Biol Chem. 2003;278(48):48204–9.

    PubMed  CAS  Google Scholar 

  34. Talebian S, Daghagh H, Yousefi B, Ȍzkul Y, Ilkhani K, Seif F, et al. The role of epigenetics and non-coding RNAs in autophagy: a new perspective for thorough understanding. Mech Ageing Dev. 2020;190:111309.

    PubMed  CAS  Google Scholar 

  35. Xiao B, Deng X, Lim GG, Xie S, Zhou ZD, Lim K-L, et al. Superoxide drives progression of Parkin/PINK1-dependent mitophagy following translocation of Parkin to mitochondria. Cell Death Dis. 2017;8(10):e3097.

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Kaminskyy V, Zhivotovsky B. Proteases in autophagy. Biochimica et Biophysica Acta (BBA) Proteins Proteom. 2012;1824(1):44–50.

    CAS  Google Scholar 

  37. Mizushima N. The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ. 2005;12(2):1535–41.

    PubMed  CAS  Google Scholar 

  38. Irving AT, Mimuro H, Kufer TA, Lo C, Wheeler R, Turner LJ, et al. The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. Cell Host Microbe. 2014;15(5):623–35.

    PubMed  CAS  Google Scholar 

  39. Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA, Parkington HC, et al. Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol. 2010;12(3):372–85.

    PubMed  CAS  Google Scholar 

  40. Ebrahimzadeh S, Ahangari H, Soleimanian A, Hosseini K, Ebrahimi V, Ghasemnejad T, et al. Colorectal cancer treatment using bacteria: focus on molecular mechanisms. BMC Microbiol. 2021;21(1):1–12.

    Google Scholar 

  41. Basak C, Pathak SK, Bhattacharyya A, Pathak S, Basu J, Kundu M. The secreted peptidyl prolyl cis, trans-isomerase HP0175 of Helicobacter pylori induces apoptosis of gastric epithelial cells in a TLR4-and apoptosis signal-regulating kinase 1-dependent manner. J Immunol. 2005;174(9):5672–80.

    PubMed  CAS  Google Scholar 

  42. Halder P, Datta C, Kumar R, Sharma AK, Basu J, Kundu M. The secreted antigen, HP 0175, of Helicobacter pylori links the unfolded protein response (UPR) to autophagy in gastric epithelial cells. Cell Microbiol. 2015;17(5):714–29.

    PubMed  CAS  Google Scholar 

  43. Li F-Y, Weng I-C, Lin C-H, Kao M-C, Wu M-S, Chen H-Y, et al. Helicobacter pylori induces intracellular galectin-8 aggregation around damaged lysosomes within gastric epithelial cells in a host O-glycan-dependent manner. Glycobiology. 2019;29(2):151–62.

    PubMed  CAS  Google Scholar 

  44. Kroemer G, Mariño G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40(2):280–93.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Yahiro K, Satoh M, Nakano M, Hisatsune J, Isomoto H, Sap J, et al. Low-density lipoprotein receptor-related protein-1 (LRP1) mediates autophagy and apoptosis caused by Helicobacter pylori VacA. J Biol Chem. 2012;287(37):31104–15.

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Zhu P, Xue J, Zhang Z-j, Jia Y-p, Tong Y-n, Han D, et al. Helicobacter pylori VacA induces autophagic cell death in gastric epithelial cells via the endoplasmic reticulum stress pathway. Cell Death Disease. 2017;8(12):1–12.

    Google Scholar 

  47. Kirst ME, Meyer DJ, Gibbon BC, Jung R, Boston RS. Identification and characterization of endoplasmic reticulum-associated degradation proteins differentially affected by endoplasmic reticulum stress. Plant Physiol. 2005;138(1):218–31.

    PubMed  PubMed Central  CAS  Google Scholar 

  48. Jungblut P, Bumann D, Haas G, Zimny-Arndt U, Holland P, Lamer S, et al. Comparative proteome analysis of Helicobacter pylori. Mol Microbiol. 2000;36(3):710–25.

    PubMed  CAS  Google Scholar 

  49. Odenbreit S, Püls J, Sedlmaier B, Gerland E, Fischer W, Haas R. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science. 2000;287(5457):1497–500.

    PubMed  CAS  Google Scholar 

  50. Kumar S, Dhiman M. Inflammasome activation and regulation during Helicobacter pylori pathogenesis. Microb Pathog. 2018;125:468–74.

    PubMed  CAS  Google Scholar 

  51. Ishikawa S, Ohta T, Hatakeyama M. Stability of Helicobacter pylori CagA oncoprotein in human gastric epithelial cells. FEBS Lett. 2009;583(14):2414–8.

    PubMed  CAS  Google Scholar 

  52. Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T, Hirata K, et al. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe. 2012;12(6):764–77.

    PubMed  CAS  Google Scholar 

  53. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36(12):2503–18.

    PubMed  PubMed Central  CAS  Google Scholar 

  54. Wen Z-p, Zeng W-j, Chen Y-h, Li H, Wang J-y, Cheng Q, et al. Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux. J Exp Clin Cancer Res. 2019;38(1):1–15.

    Google Scholar 

  55. Ma Y, Li M, Si J, Xiong Y, Lu F, Zhang J, et al. Blockade of Notch3 inhibits the stem-like property and is associated with ALDH1A1 and CD44 via autophagy in non-small lung cancer. Int J Oncol. 2016;48(6):2349–58.

    PubMed  CAS  Google Scholar 

  56. Jung CH, Seo M, Otto NM, Kim D-H. ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy. 2011;7(10):1212–21.

    PubMed  PubMed Central  CAS  Google Scholar 

  57. Karami Fath M, Azargoonjahromi A, Kiani A, Jalalifar F, Osati P, Akbari Oryani M, et al. The role of epigenetic modifications in drug resistance and treatment of breast cancer. Cell Mol Biol Lett. 2022;27(1):1–25.

    Google Scholar 

  58. Galluzzi L, Pietrocola F, Bravo-San Pedro JM, Amaravadi RK, Baehrecke EH, Cecconi F, et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015;34(7):856–80.

    PubMed  PubMed Central  CAS  Google Scholar 

  59. Liu J, Debnath J. The evolving, multifaceted roles of autophagy in cancer. Adv Cancer Res. 2016;130:1–53.

    PubMed  CAS  Google Scholar 

  60. Lock R, Kenific CM, Leidal AM, Salas E, Debnath J. Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov. 2014;4(4):466–79.

    PubMed  PubMed Central  CAS  Google Scholar 

  61. Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science. 2015. https://doi.org/10.1126/science.aaa5612.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Dupont N, Jiang S, Pilli M, Ornatowski W, Bhattacharya D, Deretic V. Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β. EMBO J. 2011;30(23):4701–11.

    PubMed  PubMed Central  CAS  Google Scholar 

  63. Wu C-Y, Wang C-J, Tseng C-C, Chen H-P, Wu M-S, Lin J-T, et al. Helicobacter pylori promote gastric cancer cells invasion through a NF-kB and COX-2-mediated pathway. World J Gastroenterol WJG. 2005;11(21):3197.

    PubMed  CAS  Google Scholar 

  64. Contreras-Zentella ML, Olguín-Martínez M, Sánchez-Sevilla L, Hernández-Muñoz R. Gastric mucosal injury and oxidative stress. Gastrointestinal tissue. Amsterdam: Elsevier; 2017. p. 65–79.

    Google Scholar 

  65. Lee KE, Khoi PN, Xia Y, Park JS, Joo YE, Kim KK, et al. Helicobacter pylori and interleukin-8 in gastric cancer. World J Gastroenterol WJG. 2013;19(45):8192.

    PubMed  CAS  Google Scholar 

  66. Wang L, Tang C, Cao H, Li K, Pang X, Zhong L, et al. Activation of IL-8 via PI3K/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells. Cancer Biol Ther. 2015;16(8):1220–30.

    PubMed  PubMed Central  Google Scholar 

  67. Chakrabarti S, Patel KD. Matrix metalloproteinase-2 (MMP-2) and MMP-9 in pulmonary pathology. Exp Lung Res. 2005;31(6):599–621.

    PubMed  CAS  Google Scholar 

  68. Zeng B, Chen C, Yi Q, Zhang X, Wu X, Zheng S, et al. N-terminal region of Helicobacter pylori CagA induces IL-8 production in gastric epithelial cells via the β1 integrin receptor. J Med Microbiol. 2020;69(3):457–64.

    PubMed  CAS  Google Scholar 

  69. Suzuki K. Characterization of exercise-induced cytokine release, the impacts on the body, the mechanisms and modulations. Int J Sports Exerc Med. 2019;5:122.

    Google Scholar 

  70. Marques MS, Melo J, Cavadas B, Mendes N, Pereira L, Carneiro F, Figueiredo C, Leite M. Afadin downregulation by Helicobacter pylori induces epithelial to mesenchymal transition in gastric cells. Front. Microbiol. 2018;9:2712.

    PubMed  PubMed Central  Google Scholar 

  71. Kim BJ, Kim JG. Substitutions in penicillin-binding protein 1 in amoxicillin-resistant Helicobacter pylori strains isolated from Korean patients. Gut Liver. 2013;7(6):655.

    PubMed  PubMed Central  CAS  Google Scholar 

  72. Liu L-P, Sheng X-P, Shuai T-K, Zhao Y-X, Li B, Li Y-M. Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression. World J Gastroenterol. 2018;24(40):4565.

    PubMed  PubMed Central  CAS  Google Scholar 

  73. Shteingauz A, Boyango I, Naroditsky I, Hammond E, Gruber M, Doweck I, et al. Heparanase enhances tumor growth and chemoresistance by promoting autophagy. Can Res. 2015;75(18):3946–57.

    CAS  Google Scholar 

  74. Shen J, Zhai J, You Q, Zhang G, He M, Yao X, et al. Cancer-associated fibroblasts-derived VCAM1 induced by H. pylori infection facilitates tumor invasion in gastric cancer. Oncogene. 2020;39(14):2961–3274.

    PubMed  CAS  Google Scholar 

  75. Sharbatdar Y, Mousavian R, Noorbakhsh Varnosfaderani SM, Aziziyan F, Liaghat M, Baziyar P, et al. Diabetes as one of the long-term COVID-19 complications: from the potential reason of more diabetic patients’ susceptibility to COVID-19 to the possible caution of future global diabetes tsunami. Inflammopharmacology. 2023;31:1–24.

    Google Scholar 

  76. Sugimoto M, Murata M, Yamaoka Y. Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an East Asian population: meta-analysis. World J Gastroenterol. 2020;26(15):1820.

    PubMed  PubMed Central  Google Scholar 

  77. Choi Y, Kim N, Yun CY, Choi YJ, Yoon H, Shin CM, et al. Effect of Helicobacter pylori eradication after subtotal gastrectomy on the survival rate of patients with gastric cancer: follow-up for up to 15 years. Gastric Cancer. 2020;23(6):1051–63.

    PubMed  Google Scholar 

  78. Piao J-Y, Kim S-J, Kim D-H, Park JH, Park S-A, Han H-j, et al. Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach. Sci Rep. 2020;10(1):15711.

    PubMed  PubMed Central  CAS  Google Scholar 

  79. Tsugawa H, Suzuki H. Oxidative stress in stomach cancer. Cancer. Amsterdam: Elsevier; 2021. p. 49–54.

    Google Scholar 

  80. 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 Biol Ther. 2006;5(7):729–35.

    PubMed  CAS  Google Scholar 

  81. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113(1):25–36.

    PubMed  CAS  Google Scholar 

  82. Yu Z, Baserga R, Chen L, Wang C, Lisanti MP, Pestell RG. microRNA, cell cycle, and human breast cancer. Am J Pathol. 2010;176(3):1058–64.

    PubMed  PubMed Central  CAS  Google Scholar 

  83. Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11(2):136–46.

    PubMed  CAS  Google Scholar 

  84. Belair C, Darfeuille F, Staedel C. Helicobacter pylori and gastric cancer: possible role of microRNAs in this intimate relationship. Clin Microbiol Infect. 2009;15(9):806–12.

    PubMed  CAS  Google Scholar 

  85. Ishiguro H, Kimura M, Takeyama H. Role of microRNAs in gastric cancer. World J Gastroenterol. 2014;20(19):5694.

    PubMed  PubMed Central  CAS  Google Scholar 

  86. Schaalan M, Mohamed W, Fathy S. MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori-induced gastric ulcer or progression to gastric cancer. Microb Pathog. 2020;149:104442.

    PubMed  CAS  Google Scholar 

  87. Wu XD, Liu WL, Zeng K, Lei HY, Zhang QG, Zhou SQ, et al. Advanced glycation end products activate the mi RNA/RhoA/ROCK 2 pathway in endothelial cells. Microcirculation. 2014;21(2):178–86.

    PubMed  CAS  Google Scholar 

  88. Sohn EJ. MicroRNA 200c–3p regulates autophagy via upregulation of endoplasmic reticulum stress in PC-3 cells. Cancer Cell Int. 2018;18(1):1–10.

    Google Scholar 

  89. Tan X, Tang H, Bi J, Li N, Jia Y. MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in gastric cancer. J Cell Biochem. 2018;119(7):5153–62.

    PubMed  CAS  Google Scholar 

  90. Shi Y, Yang Z, Zhang T, Shen L, Li Y, Ding S. SIRT1-targeted miR-543 autophagy inhibition and epithelial–mesenchymal transition promotion in Helicobacter pylori CagA-associated gastric cancer. Cell Death Dis. 2019;10(9):625.

    PubMed  PubMed Central  Google Scholar 

  91. Tang B, Li N, Gu J, Zhuang Y, Li Q, Wang H-G, et al. Compromised autophagy by MIR30B benefits the intracellular survival of Helicobacter pylori. Autophagy. 2012;8(7):1045–57.

    PubMed  PubMed Central  CAS  Google Scholar 

  92. Zhong X, Chen O, Zhou T, Lü M, Wan J. Cytotoxin-associated gene A-positive Helicobacter pylori promotes autophagy in colon cancer cells by inhibiting miR-125b-5p. Can J Infect Dis Med Microbiol. 2021;2021:1–9.

    Google Scholar 

  93. Li X, Zhu M, Zhao G, Zhou A, Min L, Liu S, et al. MiR-1298-5p level downregulation induced by Helicobacter pylori infection inhibits autophagy and promotes gastric cancer development by targeting MAP2K6. Cell Signal. 2022;93:110286.

    PubMed  CAS  Google Scholar 

  94. Chen G, Zhang M, Li Y. Research progress in the role of microRNA-155 in regulation of autophagy and diagnosis and treatment for gastric cancer. Zhong nan da xue xue bao Yi xue ban = J Central South Univ Med Sci. 2019;44(1):87–91.

    Google Scholar 

  95. Yang L, Li C, Jia Y. MicroRNA-99b promotes Helicobacter pylori-induced autophagyand suppresses carcinogenesis by targeting mTOR. Oncol Lett. 2018;16(4):5355–60.

    PubMed  PubMed Central  Google Scholar 

  96. Fan H, Jiang M, Li B, He Y, Huang C, Luo D, et al. MicroRNA-let-7a regulates cell autophagy by targeting Rictor in gastric cancer cell lines MGC-803 and SGC-7901. Oncol Rep. 2018;39(3):1207–14.

    PubMed  CAS  Google Scholar 

  97. Koustas E, Sarantis P, Kyriakopoulou G, Papavassiliou AG, Karamouzis MV. The interplay of autophagy and tumor microenvironment in colorectal cancer—ways of enhancing immunotherapy action. Cancers. 2019;11(4):533.

    PubMed  PubMed Central  CAS  Google Scholar 

  98. Cao Y, Luo Y, Zou J, Ouyang J, Cai Z, Zeng X, et al. Autophagy and its role in gastric cancer. Clin Chim Acta. 2019;489:10–20.

    PubMed  CAS  Google Scholar 

  99. Maes H, Kuchnio A, Peric A, Moens S, Nys K, De Bock K, et al. Tumor vessel normalization by chloroquine independent of autophagy. Cancer Cell. 2014;26(2):190–206.

    PubMed  CAS  Google Scholar 

  100. Dong X, Wang Y, Zhou Y, Wen J, Wang S, Shen L. Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatin via autophagy. Cell Death Discov. 2016;2(1):1–6.

    Google Scholar 

  101. Onorati AV, Dyczynski M, Ojha R, Amaravadi RK. Targeting autophagy in cancer. Cancer. 2018;124(16):3307–18.

    PubMed  Google Scholar 

  102. Koustas E, Trifylli E-M, Sarantis P, Papavassiliou AG, Karamouzis MV. Role of autophagy in cholangiocarcinoma: an autophagy-based treatment strategy. World J Gastrointest Oncol. 2021;13(10):1229.

    PubMed  PubMed Central  Google Scholar 

  103. Wang H, Li D, Li X, Ou X, Liu S, Zhang Y, et al. Mammalian target of rapamycin inhibitor RAD001 sensitizes endometrial cancer cells to paclitaxel-induced apoptosis via the induction of autophagy. Oncol Lett. 2016;12(6):5029–35.

    PubMed  PubMed Central  CAS  Google Scholar 

  104. Byun S, Lee E, Lee KW. Therapeutic implications of autophagy inducers in immunological disorders, infection, and cancer. Int J Mol Sci. 2017;18(9):1959.

    PubMed  PubMed Central  Google Scholar 

  105. Liu S, Yue C, Chen H, Chen Y, Li G. Metformin promotes Beclin1-dependent autophagy to inhibit the progression of gastric cancer. Onco Targets Ther. 2020;13:4445.

    PubMed  PubMed Central  CAS  Google Scholar 

  106. Bhattacharya U, Neizer-Ashun F, Mukherjee P, Bhattacharya R. When the chains do not break: the role of USP10 in physiology and pathology. Cell Death Dis. 2020;11(12):1–10.

    Google Scholar 

  107. Yeo SK, Paul R, Haas M, Wang C, Guan J-L. Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer. Autophagy. 2018;14(7):1214–25.

    PubMed  PubMed Central  CAS  Google Scholar 

  108. Abrahamsen H, Stenmark H, Platta HW. Ubiquitination and phosphorylation of Beclin 1 and its binding partners: tuning class III phosphatidylinositol 3-kinase activity and tumor suppression. FEBS Lett. 2012;586(11):1584–91.

    PubMed  CAS  Google Scholar 

  109. Lin S-Y, Hsieh S-Y, Fan Y-T, Wei W-C, Hsiao P-W, Tsai D-H, et al. Necroptosis promotes autophagy-dependent upregulation of DAMP and results in immunosurveillance. Autophagy. 2018;14(5):778–95.

    PubMed  CAS  Google Scholar 

  110. Le Yu WK, Gu C, Zhong D, Zhao X, Kong Y, Lin Q, et al. Obatoclax impairs lysosomal function to block autophagy in cisplatin-sensitive and-resistant esophageal cancer cells. Oncotarget. 2016;7(12):14693.

    PubMed  PubMed Central  Google Scholar 

  111. Mulcahy Levy JM, Thorburn A. Autophagy in cancer: moving from understanding mechanism to improving therapy responses in patients. Cell Death Differ. 2020;27(3):843–57.

    PubMed  Google Scholar 

  112. Yang Y, Klionsky DJ. Autophagy and disease: unanswered questions. Cell Death Differ. 2020;27(3):858–71.

    PubMed  PubMed Central  Google Scholar 

  113. Koustas E, Sarantis P, Karamouzis MV, Vielh P, Theocharis S. The controversial role of autophagy in ewing sarcoma pathogenesis—current treatment options. Biomolecules. 2021;11(3):355.

    PubMed  PubMed Central  CAS  Google Scholar 

  114. Koustas E, Papavassiliou AG, Karamouzis MV. The role of autophagy in the treatment of BRAF mutant colorectal carcinomas differs based on microsatellite instability status. PLoS ONE. 2018;13(11):e0207227.

    PubMed  PubMed Central  Google Scholar 

  115. Rosenfeld MR, Ye X, Supko JG, Desideri S, Grossman SA, Brem S, et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy. 2014;10(8):1359–68.

    PubMed  PubMed Central  CAS  Google Scholar 

  116. Boone BA, Bahary N, Zureikat AH, Moser AJ, Normolle DP, Wu W-C, et al. Safety and biologic response of pre-operative autophagy inhibition in combination with gemcitabine in patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(13):4402–10.

    PubMed  PubMed Central  Google Scholar 

  117. Mukhopadhyay S, Mahapatra KK, Praharaj PP, Patil S, Bhutia SK, editors. Recent progress of autophagy signaling in tumor microenvironment and its targeting for possible cancer therapeutics. Seminars in cancer biology. Amsterdam: Elsevier; 2021.

    Google Scholar 

  118. Ahwazi D, Neopane K, Markby GR, Kopietz F, Ovens AJ, Dall M, et al. Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965. Biochem J. 2021;478(15):2977–97.

    PubMed  CAS  Google Scholar 

  119. Kocaturk NM, Akkoc Y, Kig C, Bayraktar O, Gozuacik D, Kutlu O. Autophagy as a molecular target for cancer treatment. Eur J Pharm Sci. 2019;134:116–37.

    PubMed  CAS  Google Scholar 

  120. Vakifahmetoglu-Norberg H, Xia H-G, Yuan J. Pharmacologic agents targeting autophagy. J Clin Investig. 2015;125(1):5–13.

    PubMed  PubMed Central  Google Scholar 

  121. Rossi M, Munarriz ER, Bartesaghi S, Milanese M, Dinsdale D, Guerra-Martin MA, et al. Desmethylclomipramine induces the accumulation of autophagy markers by blocking autophagic flux. J Cell Sci. 2009;122(18):3330–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  122. Koustas E, Sarantis P, Papavassiliou AG, Karamouzis MV. The resistance mechanisms of checkpoint inhibitors in solid tumors. Biomolecules. 2020;10(5):666.

    PubMed  PubMed Central  CAS  Google Scholar 

  123. Sun S-Y. Enhancing perifosine’s anticancer efficacy by preventing autophagy. Autophagy. 2010;6(1):184–5.

    PubMed  Google Scholar 

  124. Rangwala R, Chang YC, Hu J, Algazy KM, Evans TL, Fecher LA, et al. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy. 2014;10(8):1391–402.

    PubMed  PubMed Central  CAS  Google Scholar 

  125. Zang Y, Thomas SM, Chan ET, Kirk CJ, Freilino ML, DeLancey HM, et al. The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4. Autophagy. 2012;8(12):1873–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  126. Chang H, Zou Z. Targeting autophagy to overcome drug resistance: further developments. J Hematol Oncol. 2020;13(1):1–18.

    Google Scholar 

  127. Wallin JJ, Guan J, Prior WW, Lee LB, Berry L, Belmont LD, et al. GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of docetaxel in human breast cancer models by increasing cell death in vitro and in vivo. Clin Cancer Res. 2012;18(14):3901–11.

    PubMed  CAS  Google Scholar 

  128. Wallin JJ, Edgar KA, Guan J, Berry M, Prior WW, Lee L, et al. GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011;10(12):2426–36.

    PubMed  CAS  Google Scholar 

  129. Maejima Y, Isobe M, Sadoshima J. Regulation of autophagy by Beclin 1 in the heart. J Mol Cell Cardiol. 2016;95:19–25.

    PubMed  CAS  Google Scholar 

  130. Nujić K, Banjanac M, Munić V, Polančec D, Haber VE. Impairment of lysosomal functions by azithromycin and chloroquine contributes to anti-inflammatory phenotype. Cell Immunol. 2012;279(1):78–86.

    PubMed  Google Scholar 

  131. Mauvezin C, Neufeld TP. Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. Autophagy. 2015;11(8):1437–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  132. Cui Y, Hettinghouse A, Liu C-J. Progranulin: a conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases. Cytokine Growth Factor Rev. 2019;45:53–64.

    PubMed  PubMed Central  CAS  Google Scholar 

  133. Wu Y-T, Tan H-L, Shui G, Bauvy C, Huang Q, Wenk MR, et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem. 2010;285(14):10850–61.

    PubMed  PubMed Central  CAS  Google Scholar 

  134. Zheng L, Li H, Mo Y, Qi G, Liu B, Zhao J. Autophagy inhibition sensitizes LY3023414-induced anti-glioma cell activity in vitro and in vivo. Oncotarget. 2017;8(58):98964.

    PubMed  PubMed Central  Google Scholar 

  135. Xing C, Zhu B, Liu H, Yao H, Zhang L. Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and induces apoptosis through p53 pathway in gastric cancer cell line SGC7901. Acta Biochim Biophys Sin. 2008;40(3):194–201.

    PubMed  CAS  Google Scholar 

  136. Zhang H, Chen GG, Zhang Z, Chun S, Leung BCS, Lai P. Induction of autophagy in hepatocellular carcinoma cells by SB203580 requires activation of AMPK and DAPK but not p38 MAPK. Apoptosis. 2012;17(4):325–34.

    PubMed  CAS  Google Scholar 

  137. Lohitesh K, Saini H, Srivastava A, Mukherjee S, Roy A, Chowdhury R. Autophagy inhibition potentiates SAHA-mediated apoptosis in glioblastoma cells by accumulation of damaged mitochondria. Oncol Rep. 2018;39(6):2787–96.

    PubMed  CAS  Google Scholar 

  138. Shao S, Li S, Qin Y, Wang X, Yang Y, Bai H, et al. Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia. Int J Oncol. 2014;44(5):1661–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  139. Akin D, Wang SK, Habibzadegah-Tari P, Law B, Ostrov D, Li M, et al. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors. Autophagy. 2014;10(11):2021–35.

    PubMed  PubMed Central  Google Scholar 

  140. Saini H, Sharma H, Mukherjee S, Chowdhury S, Chowdhury R. Verteporfin disrupts multiple steps of autophagy and regulates p53 to sensitize osteosarcoma cells. Cancer Cell Int. 2021;21(1):1–16.

    Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

There is no foundation for this study.

Author information

Author notes

  1. Abdullatif Akbari and Seyed Mostafa Noorbakhsh Varnosfaderani contributed equally to this work.

Authors and Affiliations

  1. Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Abdullatif Akbari & Hamidreza Zalpoor

  2. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Abdullatif Akbari, Fatemeh Aziziyan & Hamidreza Zalpoor

  3. Department of Radiology, Afzalipour Hospital, Kerman University of Medical Science, Kerman, Iran

    Seyed Mostafa Noorbakhsh Varnosfaderani

  4. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Melika Sadat Haeri

  5. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Zeinab Fathi

  6. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Fatemeh Aziziyan & Mohsen Nabi-Afjadi

  7. Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran

    Ali Yousefi Rad

  8. Saveh University of Medical Sciences, Saveh, Iran

    Yalda Malekzadegan

Authors
  1. Abdullatif Akbari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seyed Mostafa Noorbakhsh Varnosfaderani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melika Sadat Haeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zeinab Fathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fatemeh Aziziyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ali Yousefi Rad
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hamidreza Zalpoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohsen Nabi-Afjadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yalda Malekzadegan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HZ and MNA conceived the hypothesis, supervised, and designed the study. HZ, FA, AA, SMNV, MSH, ZF, AYR, YM, and MNA wrote the manuscript text. HZ and FA created the figures. HZ, MNA, SMNV, and MSH revised the manuscript. HZ, MNA, and YM edited and supervised the study. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hamidreza Zalpoor, Mohsen Nabi-Afjadi or Yalda Malekzadegan.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval and consent to participate

Not applicable.

Consent for publication

All authors have read the manuscript and given their consent for publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Akbari, A., Noorbakhsh Varnosfaderani, S.M., Haeri, M.S. et al. Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights. Human Cell 37, 139–153 (2024). https://doi.org/10.1007/s13577-023-00996-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-023-00996-2

Keywords

Search

Navigation