Table 2.
Autophagic genes involved in invasion (colonization, proliferation, tumor formation, promotion, metastasis) VS our findings.
| Gene expression changes | Cellular outcome | Effect(s) | Consequences on tumor fate | References | Our study findings | |
|---|---|---|---|---|---|---|
| 43 °C | 48 °C | |||||
| ATG5 and ATG7- RAS | Increased autophagy | Mitochondria activation | Tumor formation | 4,43 | 2.63 | 2.94 |
| 2.17 | NSC | |||||
| ATG16L1 | Autophagy deficiency | Oxidative stress | Tumor suppression | 79,80 | 1346.5 | 1164.1 |
| LC3-II degradation | Damaged mitochondria | |||||
| Inflammation induction (1β, IL-18) | 2.05 | 4.58 | ||||
| Autophagy activation | p27Kip1 coaded by CDKN1B | CDK-dependent kinase inhibitor | Tumor promotion | 81 | 423.14 | 134.83 |
| Autophagy deactivation | ATG3/7/p62 targeting | Pfkfb3 normal expression | Tumor re-proliferation | 82 | NSC | NSC |
| 2.17 | NSC | |||||
| STAT1 inhibition | p27 (CDKN1B), p21(CDKN1A) upregulation | Increase in IDO1 and Kyn receptors | Tumor dormancy | 83 | 423.1 | 134.8 |
| Rb hypophosphorylation | Increase in colony formation | |||||
| Suppress E2F transcription factor activity | Decrease in proliferation | |||||
| AMBRA1 | AMBRA1 role in the modulation of C-MYC phosphorylation and stability | Intracellular switch between autophagy and apoptosis | Colony formation | 84,85 | NSC | 2.05 |
| ATG9B mutation | Autophagy suppression | Blocked recruitment of p62-associated ubiquitinated protein for autophagosome–lysosome degradation | Tumorigenesis | 64,86 | 2.44 | 4.07 |
| GABARAPL1 down-regulation | Disruption of the intracellular transport of receptors and the autophagy pathway | Low GABARAPL1 expression was correlated with a high risk of metastasis | Metastasis | 87 | 2.04 | NSC |
| ATG10 up-regulation | Acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5 and increased autophagy | Lymphovascular invasion | Metastasis | 88 | 2.27 | 5.05 |
| RAB24 over-expression | Promote the EMT, adhesion and vasculogenic effects | Promotes the malignant phenotype | Tumor growth, metastasis, EMT activation | 88 | 2.76 | 2.23 |
| ATG5 frameshift mutations | Features of cancers with microsatellite instability (MSI) | Common in gastric and colorectal carcinomas | Tumor development by autophagy deregulation | 64 | 2.63 | 2.94 |
| CTSB | Dormancy hub gene | Strong biomarker for GBM patient’s survival | Tumor progression | 89 | 10.98 | 9.68 |
| Metastasis | ||||||
| CXCR4 activation | Independent prognostic factor for disease relapse and survival in acute myeloid leukemia (AML) patients | Increases autophagic activity and decreases | Survival | 67,90 | NSC | 3.64 |
| Colony formation | ||||||
| Cytarabine-induced apoptosis | Proliferation | |||||
| IGF-1 activation | Activated protein kinase B (AKT) | Inhibit autophagy | Induce apoptosis in drug resistant cells | 91,92 | 2.80 | 2.05 |
| INS over-expression | Precursor of insulin | Insulin signaling and the regulation of autophagy are relevant to neurodegenerative disorders | Survival | 93 | 7.81 | 15.51 |
| MAPK8 | Integration point of proliferation, differentiation, transcription regulation and development | Indispensable for TNF superfamily 10 (TNFSF)-induced autophagy | Tumor promotion | 94 | 2.96 | NSC |
| Survival | ||||||
| PIK3CG | Catalytic subunit of class I PI3Ks | Up-regulated under stress conditions | Cell remodeling and tissue failure | 95 | 9.42 | 71.92 |
| MAPK14 | Activation of MAPK14 impairs autophagosome–lysosome fusion | Phosphorylates ATG5 at threonine 75 | Survival promoting autophagy | 96,97 | 2.05 | 2.23 |
| Cell proliferation | ||||||
| Migration, Resistance to apoptosis | ||||||
| RPS6KB1 | In response to mTOR | Autophagy inhibition | Promote protein synthesis | 98 | NSC | 2.08 |
| Cell growth | ||||||
| Cell proliferation | ||||||
| DRAM2 | Is a lysosomal protein | DRAM2 overexpression induced cell migration proteins including RAC1, RHOA, RHOC, ROCK1, and decreased RHOB expression | Metastasis | 99,100 | 2.05 | NSC |
| Proliferation | ||||||
| Migration | ||||||
| Cell cycle activation | ||||||
| LAMP1 | LAMP1 is lysosomal marker | LAMP1 overexpression reversed the antitumor effects of UBL4A in pancreatic cancer | Cell proliferation | 101,102 | 3.64 | 3.08 |
| Migration | ||||||
| Invasion | ||||||
| mTOR | Key regulator of protein synthesis via 4EBP1 and p70S6K1/2 phosphorylation | Increases the translational capacity of cancer cells | Autophagy inhibition | 103 | 6.04 | 6.48 |
| Dormancy | ||||||
| Metastasis | ||||||
| RPLP0 | Belongs to the L10P family of ribosomal proteins | Affected p21 expression | Cell promotion | 104,105 | NSC | 619.5 |
| Induction | Autophagy induction (Survival) in response to RPLP deficiency stress | |||||
| G1 arrest of gastric cancer cells | ||||||
| CTSS | Is a lysosomal cysteine protease that may participate in the degradation of antigenic proteins | Cleaves some extracellular matrix (ECM) proteins | Tumorigenesis stimulation | 106,107 | 11.35 | NSC |
| Metastasis | ||||||
| ESR1 | Point mutations on ESR1 are drivers for resistance, and promote of ERα without the bound ligand | Ligand independently ER stimulation | Proliferation | 108,109 | 9.68 | 4.16 |
| Long-distance metastasis | ||||||
| Autophagy manipulation | eIF4E/eIF4GI knockdown | The decrease in ERα, SMAD5, NFkB, CyclinD1, c-MYC, and HIF1α | The decrease in EMT promoter | 59 | 1049.1 | 1904 |
| Increase in EMT inhibitors | ||||||
| The decrease in migration capability | ||||||
Significant values are in bold. NSC non significant change.