Table 1.
Summary of FFA4 involvement in cancers
| Cancer and Model | Agonist Used | Effect of FFA4 agonism | KD/KO Used | KD/KO Degree | Role of FFA1 | Ref. |
|---|---|---|---|---|---|---|
| Prostate | ||||||
| DU145 Cells | DHA, EPA EPA TUG-891, EPA TUG-891, EPA |
↓ LPA and EGF-induced
Proliferation ↓ LPA and EGF-induced p-ERK1/2, p-FAK, p-p70S6K, CCN ↓ LPA, EGF, and serum-induced proliferation ↓ LPA, and EGF-induced migration |
siRNA (FFA4) | 93% KD after 24 hr 62% KD after 48 hr |
Expressed but no role in proliferation and migration | 41,44 |
| PC-3 Cells | EPA, TUG-891 | ↓ LPA, EGF, and serum-induced Proliferation and migration | siRNA (FFA4) | Not shown | Expressed but no role in proliferation and migration | |
|
| ||||||
| Colorectal | ||||||
| Human CRC tissue | None | Positive correlation with advanced histological staging | None detected | 51 | ||
| HCT116/SW480 | GW9508 | ↑ Expression of angiogenic factors,
↑ EMT and Migration ↑ p-AKT and p-IκBα |
shRNA (FFA4) | 60 – 75% reduction | None detected | 51 |
| HT-29/LOVO | EPA, DHA | ↓Proliferation and ↑
apoptosis ↑ p-YAP and cytosolic sequestration of YAP/TAZ Sensitive to inhibition of PKA |
siRNA (FFA4)/(FFA1) | 25 – 60% reduction | Expressed and contributes to effects | 53 |
| AOM/DSS-induced murine model | Dietary EPA/DHA | ↓ YAP/TAZ and ↑ p-YAP in CRC
tumors Decreased incidence, number, and size of CRC tumors |
Expressed and contributes to effects | 53 | ||
|
| ||||||
| Lung | ||||||
| A549 | GW9508 | ↓ Proliferation, ↓ Migration, ↓ MMP-2 activity | shRNA (FFA1) | Near full | Expressed, ↑ Proliferation and Migration | 63 |
| Rat RLCNR | GW9508 | No effect on proliferation or migration | None | Expressed, ↑ Migration | 63 | |
| Mouse LL/2 | GW9508 | No effect on proliferation or migration | None | Expressed, ↑ Migration | 63 | |
|
| ||||||
| Pancreatic | ||||||
| PANC-1 | GW9508 | ↑ Migration, ↓ MMP-2 activity, ↑ Invasion | shRNA (FFA4)/(FFA1) | Near full for both | Expressed, ↓ Migration | 64 |
| Hamster HPD1NR | GW9508 | No expression detected, no effect | Expressed, ↓ Migration | 64 | ||
| Hamster HPD2NR | GW9508 | ↑ Migration | None detected | 64 | ||
|
| ||||||
| Melanoma | ||||||
| A375 | GW9508 | ↓ Proliferation and Migration | shRNA (FFA4) | > 90% | Expressed, ↑ Proliferation and Migration | 68 |
| G361 | GW9509 | ↓ Proliferation and Migration | None used | Expressed, ↑ Proliferation and Migration | 68 | |
|
| ||||||
| Breast | ||||||
| MCF-7 | GW9508, TUG-891 | No specific role, likely due to FFA1 | None used | Expressed, ↓ Proliferation and Migration | 81 | |
| MDA-MB-231 | GW9508, TUG-891 | No specific role, likely due to FFA1 | None used | Visually determined | Expressed, ↓ Proliferation and Migration | 81 |
| LA | ↑ Migration and Invasion | shRNA (FFA4) | Expressed, but contribution undetermined | 79 | ||
| EPA, DHA | No effect | KO Mice | Full (genetic KO) | Expressed | 83 | |
|
| ||||||
| Bone | ||||||
| MG-63 | GW9508 | ↑ Migration and Invasion | shRNA (FFA4) | Full | Expressed, ↓ Migration and Invasion | 85 |
| COS1NR | GW9508 | ↑ Migration | shRNA (FFA4) | Not determined | Expressed, but contribution undetermined | 85 |