The Implication of Autophagy in Gastric Cancer Progression
Abstract
:1. Introduction
2. A Review of Autophagy
3. Autophagy in Gastric Cancer
3.1. Regulation of Autophagy by MicroRNAs (miRNAs)
3.2. Regulation of Autophagy by miRNAs as Tumor Suppressor Genes
3.3. Regulation of Autophagy by miRNAs as Oncogenes
3.4. Regulation of Autophagy by Long Non-Coding RNAs (lncRNAs)
3.5. Regulation of Autophagy by PI3K/AKT/mTOR Signaling Pathway
3.6. Regulation of Autophagy by AMPK Signaling Pathway
3.7. Autophagy and Helicobacter pyloriin Gastric Cancer
3.8. Atgs in Tumorigenesis of Gastric Cancer
4. Targeted Autophagy as Putative Therapeutic Approach
4.1. Autophagy Enhancer Agents
4.2. Autophagy Inhibitors
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ATGs | Autophagy-related genes |
CAB | calcium-binding protein |
CagA | cytotoxin-associated gene A |
ceRNA | competing for endogenous RNA |
CDH1 | Cadherin 1 |
CMA | Chaperon-mediated autophagy |
CTNNA1 | Catenin Alpha 1 |
CQ | Chloroquine |
DCMI | desmethylclomipramine |
DDP | diamminedichloroplatinum |
EAC | Esophageal adenocarcinoma |
EBV | Epstein–Barr virus |
EMT | epithelial-to-mesenchymal transition |
FAP | Familial Adenomatous Polyposis |
GAPPS | stomach syndrome |
GC | Gastric cancer |
GIM | gastric intestinal metaplasia |
GSTM1 | Glutathione S-Transferase Mu 1 |
HCQ | hydroxychloroquine |
HDGC | Diffuse Gastric Cancer |
HNPCC | Hereditary Non-Polyposis Colorectal Cancer |
HOTTIP | HOXA distal transcript antisense RNA |
H. pylori | Helicobacter pylori |
IL | interleukin |
KFERQ | consensus pentapeptide of cytosolic chaperone hsc70 |
LAMP-2A | lysosomal membrane protein 2A |
lncRNAs | Long Non-Coding RNAs |
MALAT1 | metastasis-associated lung adenocarcinoma transcript 1 |
MEFs | Mouse Embryonic Fibroblasts |
MSI | microsatellite instability |
mTOR | mammalian target of rapamycin |
PE | phosphatidylethanolamine |
PGE2prostaglandin | E2 |
PPIs | Proton-pump inhibitors |
UVRAG | Ultraviolet radiation resistance-associated gene |
VacA | vacuolating cytotoxin |
VEGF | Vascular endothelial growth factor |
5-FU | 5-fluorouracil |
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ATGs | Human Orthologue | Autophagy Step | Molecular Function |
---|---|---|---|
Atg1 | ULK1/2 | Induction | Kinase |
Atg2 | ATG2A, ATG2B | Nucleation | Protein binding |
Atg3 | ATG3 | Elongation | Ubiquitin-like ligase |
Atg4a | ATG4A, ATG4B | Elongation | Cysteine-type endopeptidase |
Atg4b | ATG4C | Elongation | Cysteine-type endopeptidase |
Atg5 | ATG5 | Maturation | Ubiquitin-like ligase |
Atg6 | BECN1 | Nucleation | Kinase |
Atg7 | ATG7 | Elongation | Ubiquitin-activating enzyme |
Atg8a | GABARAP | Elongation | Ubiquitin-like |
Atg8b | MAP1LC3C, MAP1LC3B2 | Elongation | Ubiquitin-like modifying enzyme |
Atg9 | ATG9A, ATG9B | Nucleation | Protein binding |
Atg10 | ATG10 | Maturation | Ubiquitin-like ligase |
Atg12 | ATG12 | Maturation | Ubiquitin-like |
Atg13 | ATG13 | Induction | Protein kinase binding |
Atg14 | ATG14 | Nucleation | Kinase |
Atg16 | ATG16L1, ATG16L2 | Maturation | Ubiquitin-like ligase |
Atg17 | RB1CC1 | Induction | Protein kinase binding |
Atg18a | WIPI2 | Nucleation | PIP2 binding |
Atg101 | ATG101 | Induction | Protein binding |
Agents | Mechanism of Action | Target |
---|---|---|
Rapamycin | mTORC1 inhibitor | Formation of Autophagosome |
Deforolimus | mTORC1 inhibitor | Formation of Autophagosome |
Temsirolimus | mTORC1 inhibitor | Formation of Autophagosome |
Everolimus | mTORC1 inhibitor | Formation of Autophagosome |
GDC-0941 | PI3K Class I inhibitor | Formation of Autophagosome |
GDC-0980 | PI3K and mTORC1 inhibitor | Formation of Autophagosome |
Tat–Beclin-1 peptide | Releases Beclin-1 into cytoplasm | Formation of Autophagosome |
Perifosine | AKT inhibitior | Formation of Autophagosome |
Metformin | AMPK activator | Formation of Autophagosome |
fluspirilene | Antagonists of L-type Ca2+ channels | Lysosome |
cepharanthine | Natural alkaloid | Autophagic flux |
isoliensinine | Natural alkaloid | Autophagic flux |
Agents | Mechanism of Action | Target |
---|---|---|
Chloroquine (CQ) | Neutralizes the acidic pH of intracellular vesicles | Lysosome |
Hydroxy-chloroquine (HCQ) | CQ derivative | Lysosome |
Bafilomycin A1 | Inhibition of lysosomal acidification | Lysosome |
Azithromycin | Inhibition of lysosomal acidification | Lysosome |
Concanamycin A | Inhibition of lysosomal acidification | Lysosome |
3-Methyladenine (3-MA) | PI3K- Class III inhibitor | Formation of Autophagosome |
Wortmannin | PI3K- Class III inhibitor | Formation of Autophagosome |
LY294002 | PI3K- Class III inhibitor | Formation of Autophagosome |
LY3023414 | PI3K- Class III inhibitor | Formation of Autophagosome |
SAR405 | Vps18 and Vps34) inhibitor | Formation of Autophagosome |
SB203580 | Inhibit trafficking of Atg9 | Formation of Autophagosome |
Paclitaxel | Microtubule stabilizer inhbits phosphorylation of VPS34 | Formation of Autophagosome |
SAHA | Inhibit fusion of autophagosome and lysosome | Formation of Autophagosome |
Sputin-1 | (USP10) and (USP13) inhibitor | Formation of Autophagosome |
NSC185058 | ATG4 inhibitor | Formation of Autophagosome |
Verteporfin | Alter lysosomes accedification | Formation of Autophagosome |
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Koustas, E.; Trifylli, E.-M.; Sarantis, P.; Kontolatis, N.I.; Damaskos, C.; Garmpis, N.; Vallilas, C.; Garmpi, A.; Papavassiliou, A.G.; Karamouzis, M.V. The Implication of Autophagy in Gastric Cancer Progression. Life 2021, 11, 1304. https://doi.org/10.3390/life11121304
Koustas E, Trifylli E-M, Sarantis P, Kontolatis NI, Damaskos C, Garmpis N, Vallilas C, Garmpi A, Papavassiliou AG, Karamouzis MV. The Implication of Autophagy in Gastric Cancer Progression. Life. 2021; 11(12):1304. https://doi.org/10.3390/life11121304
Chicago/Turabian StyleKoustas, Evangelos, Eleni-Myrto Trifylli, Panagiotis Sarantis, Nikolaos I. Kontolatis, Christos Damaskos, Nikolaos Garmpis, Christos Vallilas, Anna Garmpi, Athanasios G. Papavassiliou, and Michalis V. Karamouzis. 2021. "The Implication of Autophagy in Gastric Cancer Progression" Life 11, no. 12: 1304. https://doi.org/10.3390/life11121304
APA StyleKoustas, E., Trifylli, E. -M., Sarantis, P., Kontolatis, N. I., Damaskos, C., Garmpis, N., Vallilas, C., Garmpi, A., Papavassiliou, A. G., & Karamouzis, M. V. (2021). The Implication of Autophagy in Gastric Cancer Progression. Life, 11(12), 1304. https://doi.org/10.3390/life11121304