Table 3 Autophagic genes involved in cell death (autophagic or apoptotic) VS our findings.
Gene expression changes | Cellular outcome | Effect(s) | Consequences on tumor fate | References | Our study findings | |
|---|---|---|---|---|---|---|
43 °C | 48 °C | |||||
Dormancy activation | P53 overexpression induced by Cdkn1b | Pentose phosphate pathway destruction | Cell death | 3.24 | NSC | |
Increased ROS | Dormancy induction by IFN-b | |||||
FasL (CD95L or CD178), TRAIL and TNF-α activation | DISC formation | Caspase-3, 6 and 7 activation | Directly cell death | 408.7 | 151.6 | |
Bid change into tBid | Mitochondria dependent apoptotic cell death | 4.07 | − 4.10 | |||
4.10 | − 2.90 | |||||
Autophagy inhibition | ATG7 depletion | Accumulation of damaged mitochondria | The killing of dormant cells | 2.17 | NSC | |
Increase of ROS | Does not affect cell metastasis and proliferation | |||||
Increase of apoptosis | ||||||
Autophagy activation | TMEM166 overexpression | High LC3II/LC3I | Autophagy and apoptosis regulator (autophagic and apoptotic cell death) | 2.27 | 295.1 | |
Vacuolization | ||||||
Mitochondria membrane permeabilization | ||||||
GABARAPL2/ULK upregulation | Necessary to maturation of two layers membranous vesicles | Shrinkage of tumor volume in complex with ULK2 | Apoptotic cancer cell death | 3.22 | 2.12 | |
IRGM KO | p47 dependent GTPase | Negative regulation of IFN signaling | Inhibition of autophagic cell death | 46.37 | NSC | |
ATG16L2 | Methylation of ATG16L2 | Downregulation of autophagy | Autophagic cancer cell death | 29.55 | 21.63 | |
Patients survival | ||||||
Inherent ATG5 or autophagy KO | Autophagy deficiency | – | Increase apoptotic cell death | 2.63 | 2.94 | |
Increase of Bax and Bak1 | Intrinsic pathway of apoptosis (mitochondria) | Indirectly effect on autophagy by inactivation of BaK1 and Bax | Increase cancer cell apoptosis | 492.85 | 299.21 | |
Bid and PUMA (apoptosis-associated genes) | BID acts as molecular link between apoptosis and autophagy | Contribute to identifying the molecular mechanism by which autophagy drives cells to death | Autophagic cell death | 3.35 | 2.42 | |
PUMA is certain substrate for CMA | ||||||
DAPK1 | One of the most important genes in intra/extra cellular apoptotic pathways | ARHI dependent | Tumor suppressor | 2280.29 | 1453.18 | |
Apoptotic cell death | ||||||
PTEN | Negative regulator of PI3K/AKT/mTORC1 | Autophagy activation, PI3K/Akt inhibition, PI3K/AKT/mTORC1 inhibition | Tumor suppressor | 35.38 | 23.02 | |
PTEN | Indirectly positive autophagy regulator | PTEN inhibitors (Tsc1 or Tsc2, p27) and Foxo3a | Escape from dormancy | 35.38 | 23.02 | |
PTEN | Tumor suppressor | Apoptosis modulators DRAM, DAPk and DRP-1, PTEN, E93, Akt/PKB, and mTOR), Bcl-2 family proteins, TRAIL and beclin 1 | Autophagy act as upstream control of apoptosis death | 35.38 | 23.02 | |
GAA deficiency | Lysosomal hydrolysis of glycogen to glucose (glycogen storage disease II, or Pompe) | Accumulation of abnormal proteins and organelles due to inhibition of autophagy | Cell death | NSC | 3.69 | |
Autophagy abortion | DRAM1 overexpression | By p53 | Apoptotic death | 4.36 | 2.65 | |
