Table 1.
Pivotal genes/proteins participating in the process of autophagy and BCBM
| Genes/Proteins | Autophagy in BC | BC | BCBM | Functions | References |
|---|---|---|---|---|---|
| Beclin 1 | Lethal autophagy | Tumorigenesis | Not known | Heterozygous disruption of the beclin 1 is found in human BC, a tumor suppressor. It also enhances BC stem-like/progenitor cells. | 69, 70 |
| ATG4A | Survival autophagy | Tumorigenesis | Not known | ATG4A promotes BC stem-like phenotype. | 59 |
| ATG5 | Lethal autophagy | Inhibition of tumorigenesis | Reduced BCBM | Downregulation of ATG5-dependent macroautophagy linked with BC growth and metastasis to the brain. | 39, 71 |
| ATG3, ATG7 | Survival autophagy | Tumorigenesis | Not known | Promotes the survival of dormant BC cells and metastatic tumor recurrence. | 58, 72 |
| LC3 | Survival autophagy | Tumorigenesis | Not known | TNBC cell proliferation, survival, migration, and invasion, and may contribute to tumor growth and progression. | 73 |
| LC3B | Survival autophagy | Tumorigenesis | Elevated in BCBM | Elevated levels are linked with shorter survival in TNBC patients. | 68 |
| P62/SQSTM1 | Lethal autophagy | Tumorigenesis | Not known | Interacts with vimentin to enhance BC metastasis. Metastatic dormancy of BC. | 72, 74 |
| ULK1 | Lethal autophagy | Inhibition of tumorigenesis | Not known | ULK1 phosphorylates Exo70 to suppress BC metastasis. Prognostic marker of BC patients. | 75, 76 |
| BIRC5 | Lethal autophagy | Inhibition of tumorigenesis | Not known | Levels of BIRC5 and ATG7 were inversely correlated. A novel ATG12-ATG5 conjugate interactor. It induces lethal autophagy in BC cells. | 77 |
| MTA1 | Survival autophagy | Tumorigenesis | Not known | A novel regulator of autophagy induces tamoxifen resistance in BC cells. | 78 |
| CEMIP and BiP | Survival autophagy | Tumorigenesis | Not known | Overexpressed, protective autophagy is observed in response to hypoxia, associated with tumor progression. | 79 |
| KISS1 | Lethal autophagy | Inhibition of metastases development | Reduced expression of KISS1, enhances BCBM | Astrocytes promote BCBM via KISS1-mediated autophagy | 80, 81 |
| GRP94 | Survival autophagy | Tumorigenesis | Induced BCBM | It is overexpressed in BCBM, involved in autophagy-mediated survival in endoplasmic reticulum stress. | 82 |
| FIP200/ATG17 | Survival autophagy | Tumorigenesis | Protein expression higher in BCBM | A significant correlation is observed between higher FIP200/ATG17 expression in primary-BC tumors and shorter disease-free survival. | 68 |
| ST6GALNAC5 | Not known | Tumorigenesis | Induced BCBM | It enhances BC cell adhesion to brain endothelial cells and their passage through the BBB. | 83 |
| Semaphorin 4D (SEMA4D) | Not known | Tumorigenesis | Induced BCBM | Semaphorin 4D/plexin B1 interactions mediate BCBM by promoting CTC transmigration through the BBB. | 84 |
| PTEN | Lethal autophagy | Inhibition of metastases development | Downregulated in BCBM | PTEN loss and elevated PI3K/AKT signaling are found in BCBM patients. | 85 |