Autophagic Genes Involved in Cell Death (Autophagic, Apoptotic) |
Dormancy activation | P53 overexpression induced by Cdkn1b | Pentose phosphate pathway destruction, Increased ROS | Cell death, Dormancy induction by IFN-b | (Liu et al., 2018b) |
FasL (CD95L or CD178), TRAIL, and TNF-α activation | DISC formation | Cas-3, 6 and 7 activation, Bid change into tBid | Directly cell death, Mitochondria-dependent apoptotic cell death | (Su et al., 2015) |
Autophagy inhibition | ATG7 depletion | Accumulation of damaged mitochondria, Increase of ROS, Increase of apoptosis | Killing of dormant cells, Has no any effect on cell metastasis and proliferation | (Vera-Ramirez et al., 2018) |
Autophagy activation | TMEM166 overexpression | High LC3II/LC3I Vacuolization Mitochondria membrane permeabilization | Autophagy and apoptosis regulator (autophagic and apoptotic cell death) | (Wang et al., 2007a) |
IRGM | — | Negative regulation of IFN signaling | Autophagic cell death | (King et al., 2011) |
Increase of Bax and Bak1 | Inactivation of BaK1 and Bax | Intrinsic pathway (mito), indirect effect on the autophagy | Increase cancer cell apoptosis | (Karch et al., 2017; Lindqvist and Vaux 2014) |
DAPK1 | — | ARHI-dependent | Tumor suppressor, Apoptotic cell death | (Wu et al., 2013; Tong et al., 2018) |
PTEN | Autophagy activation | PI3K/Akt inhibition, PI3K/AKT/mTORC1 inhibition | Tumor suppressor | (Gundara et al., 2012) |
PTEN | PTEN inhibitors | Tsc1 or Tsc2, p27 and Foxo3a | Escape from dormancy | (Richmond et al., 2015; Chen et al., 2018a) |
PTEN | Apoptosis modulator activation | DRAM, DAPk and DRP-1, PTEN, E93, Akt/PKB and mTOR), Bcl-2 family proteins, TRAIL and bec-1 | Autophagy acts as upstream control of apoptosis death | (Wang et al., 2007a) |
Autophagy abortion | DRAM1 overexpression | By p53 | Apoptotic death | (Criollo et al., 2009) |
Autophagic Genes Involved in Invasion (Colonization, Proliferation, Tumor Formation, Promotion, Metastasis) |
ATG5 and ATG7- RAS | Increased autophagy | Mitochondria activation | Tumor formation | (Li et al., 2020; Gundara et al., 2012) |
Autophagy inhibition | Cas-3/ATG16L1 complex formation | Sustained intracellular stress and pathogen | Disease or tumor promotion | (Murthy et al., 2014) |
Autophagy deficiency | ATG4D deficiency | Intracellular LC3-B/P62 accumulation, Autophagosome formation abortion | Disease and tumor promotion | (El Andaloussi et al., 2017) |
Autophagy activation | ATG5/7 increased | — | Increase in colonization | (Washington et al., 2015) |
Autophagy activation | p27Kip1 coded by CDKN1B | CDK-dependent kinase inhibitor | Tumor promotion | (Cusan et al., 2018) |
Autophagy deactivation | ATG3/7/p62 targeting | Pfkfb3 normal expression | Tumor reproliferation | (La Belle Flynn et al., 2019; Mathew et al., 2009) |
STAT1 inhibition | p27 (CDKN1B), p21(CDKN1A) upregulation | Increase in IDO1 and Kyn receptors, Rb hypophosphorylation, suppress E2F transcription factor activity | Tumor dormancy, Increase in colony formation, Decrease in proliferation | (Wu et al., 2012) |
ATG9B | Autophagy deregulation | — | Tumorigenesis | (Li et al., 2020; Kang et al., 2009) |
Autophagy manipulation | eIF4E/eIF4GI knockdown | Decrease in ERα, SMAD5, NF-kB, CyclinD1, c-MYC, and HIF1α | Decrease in EMT promoter, Increase in EMT inhibitors, Decrease in migration capability | (Attar-Schneider et al., 2016) |
Autophagic Genes Involved in Dormancy (Suppression, Inhibition, Resistance to Anoikis, Invasiveness and Colonization, Recurrence) |
Activation of Nix/ BNIP3L+ GABARAPL1+ GABARAP | Autophagy activation and deletion of damaged Mitochondria | Increase ROS | Tumor suppression | (Poillet-Perez et al., 2015) |
ATG5 and ATG7 deletion | Autophagy inhibition | Oxidative stress, Damaged Mitochondria | Tumor suppression | (La Belle Flynn et al., 2019) |
ATG16L1, Bec-1, and LC3-II degradation | Autophagy deficiency | Oxidative stress Damaged Mitochondria, Inflammation (IL-1β, IL-18) | Tumor suppression | (Fernández and López-Otín 2015; Maruyama and Noda, 2017) |
High Atg4B | Autophagy inhibition | LC3-PE degradation, LC3 sequestration in cytosol | Tumor suppressive | (Galluzzi et al., 2017) |
Autophagy activation | DNA damage | Atg4a and Atg4c/p53 contribution | Tumor suppression by p53-mediated apoptosis | (Kenzelmann Broz et al., 2013) |
Autophagy deficiency | ATG16L1 overexpression (nonspecific organs) | — | Tumor formation suppression | (Capparelli et al., 2012) |
Autophagy deficiency | UVRAG upregulation | — | Tumor suppression | (Liang et al., 2006) |
Autophagy deficiency | ATG5 and ATG12 deficiency | Decreased survival capacity to metabolic stress | Tumor suppression (decrease in colonization and survival capability) | (Maes et al., 2014) |
Dormancy activation | P53 overexpression induced by Cdkn1b | Pentose phosphate pathway destruction, Increased ROS | Cell death, Dormancy induction by IFN-b | (Liu et al., 2018c) |
ER stress | K-RAS dependent Eif2ak3−/− MEFs | Decrease in VCIP and PDGFRB (angiogenic stabilizer) | Tumor suppression, ECM destruction, Vast hemorrhage | (Cubillos-Ruiz et al., 2017) |
BBC3/ HSPA8(HSC70) complex formation | CMA | Cargo delivery to lysosome | Tumor protection by autophagy | (Xie et al., 2015) |
IFN-γ/STAT1 activation | Downregulation of cyclin E, A, D1, 2, 3 | Downregulation of CDK4 and CDK6 | Cell cycle arrest, Cancer cell dormancy | (Dimco et al., 2010; Schmitt et al., 2012) |
Inherent ATG5 or autophagy KO | Intracellular inherent autophagy | Postpone recurrence | Recurrence, chemotherapy desensitization, increase of dormancy frequency | (Aqbi et al., 2018a) |
ER stress | EIF2AK3 suppression | Upregulation of FGF2, VEGF, and IL-6 Downregulation of THBS1, CXCL14, and CXCL10 | Suppression of angiogenesis and tumor promotion Tumor suppression | (Cubillos-Ruiz et al., 2017) |