Table 2.
Different mechanisms by which metformin inhibits invasion and metastasis in different cancers
| Cancer type | Pathways | Cell line | Animal experiment | Ref. |
|---|---|---|---|---|
| Breast cancer | COX2 signaling | MDA-MB-231 | NO | [77] |
| MiR-200c/AKT signaling | MDA-MB-231, MCF-7, T-47-D and BT549 | YES | [52] | |
| Scribble/MST1, LATS1/YAP signaling | MCF7 | YES | [86] | |
| AMPK signaling | MDA-MB-231 and MCF-7 | YES | [42] | |
| TNBC | TGF-β signaling | MCF7, MDA-MB-468, BT-549, SUM159PT, HS578T, MDA-MB-436 and MDA-MB-231 | NO | [64] |
| ERK/RAD51 signaling | MDA-MB-231 and Hs578T | YES | [67] | |
| Glioblastoma | AKT/PI3K signaling | SF268 and U87 | NO | [60] |
| AMPK/mTOR signaling | A172 | NO | [32] | |
| EMT signaling | GBM-TS | YES | [49] | |
| NSCLC | miR-381/YAP signaling | A549, H1299, Calu6, H520 and 95-D | YES | [53] |
| IRF-1/YAP signaling | A549, H1299, Calu6 and H520 | YES | [85] | |
| Cervical cancer | MALAT1/miR-142-3p signaling | SiHa and HeLa | YES | [79] |
| TGF-β/mTOR/p70S6K | HeLa and SiHa | NO | [62] | |
| HIF-1α/CAIX signaling | C-4I (CRL-1954) and HTB-35 (SiHa) | NO | [87] | |
| PI3K/AKT/mTOR signaling | CaSki, SiHa and HeLa | YES | [61] | |
| insulin signaling | SiHa and HeLa | YES | [71] | |
| ESCC | EMT signaling | TE-9 | YES | [56] |
| AKT/NF-κB signaling | TE1, TE2, TE4, TE5, TE6, TE8, TE10, TE11, TE14, TE15 and T.Tn | YES | [68] | |
| Esophageal cancer | AMPK/mTOR signaling | KYSE150 and KYSE410 | YES | [35] |
| Rectal cancer | EMT signaling | SW837, SW1463, HCT116 and LS513 | YES | [48] |
| Liver cancer | AMPK/TIP30 signaling | MHCC97H | YES | [38] |
| AMPK signaling | Hep3B, C3A and HuH-7 | NO | [33] | |
| HIF-1α signaling | MHCC97H | YES | [89] | |
| AMPK/PTEN/AKT signaling | HepG2 and SMMC7721 | YES | [58] | |
| PI3K/AKT/mTOR signaling | HepG2 and Bel-7402 | YES | [59] | |
| Pancreatic cancer | LKB1/Snail signaling | Capan-1, Capan-2, PANC-1, Mia paca-2, CFPAN-1, BxPC-3, HPAC, SW1990, ASPC-1 and HEK-293T | NO | [50] |
| miRNA signaling | AsPC-1, AsPC-1-GTR, MiaPaCa-2, and MiaPaCa-2-GTR | YES | [78] | |
| TGF-β1 signaling | Panc-1 and BxPC-3 | YES | [63] | |
| MAPK signaling | SKOV3 and hey | NO | [92] | |
| ECM signaling | SKOV3 and HO8910-PM | YES | [94] | |
| AMPK/H3K27me3 signaling | SKOV3, ES2 and A2780 | NO | [36] | |
| AMPK/VEGF signaling | A2780 | YES | [40] | |
| SPHK1 signaling | TYKnu, CAOV3, Kuramochi and OVCAR5 | YES | [93] | |
| Lung cancer | IL-6 signaling | H1650 and PC-9 | YES | [74] |
| Melanoma | AMPK/ERK signaling | A375, Mel Z, Mel IL, Mel MTP and Mel Me | NO | [65] |
| AMPK/p53 signaling | A375, WM9, SKMel28, 1205Lu, Mel501 and Mewo | YES | [39] | |
| Gastric cancer | VEGF signaling and EMT signaling | Clinical data | NO | [72] |
| HIF-1α/PKM2 signaling | SGC7901 and BGC-823 | NO | [88] | |
| non-coding RNA H19 signaling | AGS and SGC7901 | NO | [82] | |
| Prostate cancer | COX2/PGE2/STAT3 signaling | PC-3 and 22RV1 | YES | [75] |
| GTPase Rac1 signaling | PC3 and DU145 | NO | [90] | |
| FAK signaling | PC-3 and C4-2B | NO | [83] | |
| Human fibroblastoma | Ca2+/PKCα/ERK/JNK/AP-1 signaling | HT-1080 | NO | [91] |
| Bladder Cancer | STAT3 signaling | T24 and J82 | YES | [76] |
| Colorectal cancer | EMT signaling | SW480 and HCT116 | NO | [51] |
| Endometrial cancer | AKT/ERK (1/2) signaling | ECC-1 | NO | [66] |
| Cholangiocarcinoma | AMPK/mTOR/FAK signaling | KKU-100 and KKU-452 | NO | [34] |
| AMPK/IGF-1R/IRS/TSC2 signaling | SNU-245 and SNU-1196 | NO | [41] | |
| Colorectal cancer | FAK signaling | SW-480 and HT-29 | NO | [84] |
TNBC: Triple-negative breast cancer; NSCLC: Non-small cell lung cancer; ESCC: Esophageal squamous cell carcinoma.