Table 1.
E3 ubiquitin ligases that played important roles in the multiple steps of breast cancer metastasis .
| E3 | Substrate | Inhibit/Promote Metastasis | Cellular Function | Molecular Pathway | References |
|---|---|---|---|---|---|
| Arkadia | Ski | Inhibit | EMT | TGF-beta | (33) |
| ASB13 | SNAI2 | Inhibit | Migration | Hippo–YAP | (34) |
| BCA2 | Autoubiquitination | Promote | Migration and invasion | EGFR | (35, 36) |
| Cbl | FAK and EGFR | Promote/inhibit | Cell detachment/EMT and migration | FAK, RANKL/RANK EGFR-ERK/Akt | (37–40) |
| CHIP | Pfn1 | Promote | Migration | ROCK1/Pfn1 | (41, 42) |
| COP1 | c-Jun | Inhibit | Migration | ETV1, GSK3β/c-Jun | (43, 44) |
| Cullin1 | N/A | Promote | EMT, migration, invasion, and tube formation | PI3K/AKT, NF-κB | (45) |
| Cullin3/SPOP | PR, Erα | Inhibit | Migration | PR, ERα | (46, 47) |
| Cullin3/KCTD5 | N/A | Promote | Migration and invasion | TRPM4 | (48) |
| Cullin7 | N/A | Promote | Invasion | N/A | (49) |
| FBXW7 | NICD1/Notch1 | Promote/inhibit (indirect evidence) | Migration and invasion | NOTCH/p62 | (50, 51) |
| FBXL8 | N/A | Promote | Migration and invasion | CCND2/IRF5 | (52) |
| FBXL14 | CDCP1 | Inhibit | EMT, migration, and invasion | PI3K/AKT | (53) |
| FBXO11 | SNAI1 | Inhibit | Emt | SNAI1 and p53/p21/BCL2 | (54, 55) |
| FBXO22 | HDM2 | Inhibit | Migration and invasion | p53/p21, SNAIL | (56) |
| FBXO31 | Slug | Inhibit | Invasion | N/A | (57) |
| FBXO32 | KLF4 | Promote | EMT, migration, and invasion | N/A | (58) |
| GP78 | HSPA5 | Inhibit | Migration and invasion | N/A | (59, 60) |
| HACE1 | Rac1 | Inhibit | Migration and invasion | N/A | (61) |
| HectD1 | ACF7 | Inhibit | EMT, migration, and invasion | N/A | (62) |
| HERC2 | BRCA1 | Promote (indirect evidence) | Invasion (indirect evidence) | BRCA1 | (63) |
| HERC4 | LATS1 | Promote | Migration and invasion | LATS1 | (64) |
| HRD1 | IGF-1R | Inhibit | EMT, migration, and invasion | IL6/NF-κB | (65) |
| ITCH | c-Jun, p73, p63, and ErbB4; RASSF1A; histone H1.2 | Promote | EMT and invasion | Hippo | (66–68) |
| MARCH5 | N/A | Promote | Migration and invasion | Mitochondrial | (69) |
| MDM2 | P53; RB; Foxo3a | Promote | EMT, migration, and invasion | p53/p21 | (70–73) |
| MEX3C | PTEN | Promote | EMT | TWIST1, SNAI1, and YAP1 | (74) |
| NEDD4 | Robo1 | Promote | Migration and invasion (indirect evidence) | FAK and Src | (75–77) |
| NKLAM | N/A | Inhibit | Tumor immunity | NK killing activity | (78) |
| NRBE3 | RB | Promote | Migration and invasion | E-cadherin | (79) |
| NRDP1 | ErbB3 and ErbB4 | Inhibit (indirect evidence) | Migration and invasion (indirect evidence) | ER | (80) |
| Parkin | HIF-1α | Inhibit | Migration and invasion | HRE/VHL | (81) |
| PDZRN4 | Kidins220 (predict) | Inhibit | Migration and invasion | N/A | (82) |
| PPIL2 | SNAI1 | Inhibit | EMT, migration, and invasion | SNAI1 | (83) |
| RNF8 | TWIST | Promote | EMT, migration, and invasion | TWIST; GSK3β | (84, 85) |
| RNF20 | Histone H2B | Promote (luminal)/inhibit (in basal-like) | Migration | ER (in luminal) and NF-kB (in basal-like) | (86, 87) |
| RNF144A | HSPA2 | Inhibit | Migration and invasion | HSPA2 | (88) |
| RNF208 | Vimentin | Inhibit | Migration and invasion | Vimentin | (89) |
| SIAH1/2 | p27 | Promote | Migration and invasion | Rb | (90) |
| SKP2 | AKT | Promote | Indirect evidence | PI3K/AKT | (91) |
| SCF-JFK | ING4 | Promote | EMT, invasion, and angiogenesis | NF-κB | (92) |
| β-Trcp | PRLr/βCatenin | Promote | EMT, migration, and invasion | PRL,Wnt | (93, 94) |
| Smurf1 | RhoA p120-catenin and TRAF4 | Promote | EMT, migration, and invasion | TGFβ | (95–99) |
| Smurf2 | Smurf1, CNKSR2 | Promote/inhibit | Migration and invasion | TGFβ, PI3K/AKT | (100–104) |
| TRAF6 | H2AX | Promote | Migration and invasion | HIF1α | (105, 106) |
| TRIM8 | Erα | Inhibit | Migration and invasion | Erα | (107) |
| TRIM11 | Erα | Promote | Migration | Erα | (108) |
| TRIM44 | N/A | Promote | Migration | NF-κB | (109) |
| TRIM47 | N/A | Promote | EMT, migration, and invasion | PI3K/Akt | (110) |
| UBR5 | N/A | Promote | EMT, migration, and invasion | STAT3, TGFα, P38MAPK | (111, 112) |
| UBR7 | H2B | Inhibit | EMT, migration, and invasion | Wnt/β-catenin | (113) |
| WWP1 | CXCR4 (indirect evidence) | Inhibit | Migration | TGFβ/Smad | (114) |
| xIAP | TAK1 | Promote | Invasion | TGFβ/Smad | (115) |
| UBE2O | AMPkα2 | Promote | EMT, migration, invasion, and stemness | AMPK/mTOR | (116) |
ASB13, ankyrin repeat and SOCS box containing 13; BCA2, breast cancer associated gene 2; Cbl‐b, Cbl proto-oncogene B; CHIP, STIP1 homology and U-box containing protein 1; CXCR4, C-X-C motif chemokine receptor 4; SPOP, speckle type BTB/POZ protein; KCTD5, K+ channel tetramerization domain 5; FBXW7, F-box and WD repeat domain containing 7; FBXL8, F-box and leucine rich repeat protein 8; FBXL14, F-box and leucine rich repeat protein 14; FBXO11, F-box protein 11; FBXO22, F-box protein 22; FBXO31, F-box protein 31; FBXO32, F-box protein 32; GP78, autocrine motility factor receptor; HACE1, HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1; HECTD1, HECT domain E3 ubiquitin protein ligase 1; HERC2, HECT and RLD domain containing E3 ubiquitin protein ligase 2; HERC4, HECT and RLD domain containing E3 ubiquitin protein ligase 4; MARCHF5, membrane associated ring-CH-type finger 5; MEX3C, mex-3 RNA binding family member C; NKLAM, Natural killer lytic-associated molecule; NRBE3, New RB E3 ubiquitin ligase; NRDP1, also known as RNF41, ring finger protein 41; Parkin, parkin RBR E3 ubiquitin protein ligase; PDZRN4, PDZ domain containing ring finger 4; PPIL2, peptidylprolyl isomerase like 2; RNF, RING Finger Protein; RASSF1, Ras association domain family member 1; SIAH1/2, siah E3 ubiquitin protein ligase 1 and 2; SKP2, S-phase kinase associated protein 2; SCF, Skp-Cullin-F-box) complex; β-Trcp, beta-transducin repeat containing E3 ubiquitin protein ligase; SMURF1 and SMURF2, SMAD specific E3 ubiquitin protein ligase 1 and 2; TRAF6, TNF receptor associated factor 6; TRIM8, TRIM11, TRIM44, TRIM47: tripartite motif containing 8, 11, 44 and 47; UBR5 and UBR7, ubiquitin protein ligase E3 component n-recognin 5 and 7; TWIST, twist family bHLH transcription factor 1; WWP1, WW domain containing E3 ubiquitin protein ligase 1; xIAP, X-linked inhibitor of apoptosis; UBE2O, ubiquitin conjugating enzyme E2 O; N/A, Not Available in the reference literature.