Table 2.
Evidence of hybrid E/M phenotypes in various in vitro, in vivo models and clinical studies.
| Model | Effect | Mechanism | Ref. |
|---|---|---|---|
| In Vitro Studies | |||
| HMLER cells | Hybrid EMT, stemness | ↓Krt 5, ↓Krt 8, ↓pan-cytokeratin, ↓E-cad, ↑vimentin, ↑ZEB1, ↑SNAI1 | [17] |
| Human lung adenocarcinoma (DFCI032, H1650, H1693, HCC827) cells | Hybrid EMT, invasion, migration | E-cad+, Vimentin+, ↑ZEB1, ↑SNAI2, ↑miR-34a | [18] |
| Human lung adenocarcinoma (H1975) cells | Cell migration, hybrid EMT | ↓GRHL2, ↓OVOL2, ↓E-cad (CDH1), ↑ZEB1 | [59] |
| IBC (SUM149, Mary-X and FC-IBC02) cells | Co-expression of E/M phenotype, Stemness | CD44+, ↑TWIST1, ↑E-cad, ↑DSC2, ↑Vimentin | [65] |
| HMLER cells | Hybrid EMT, plasticity, stemness, mammosphere formation | CD24+/CD44+, ↑ALDH1 | [66] |
| Human mammary epithelial (MCF 10A) cells | Hybrid EMT | E-cadmedium, vimentinmedium, SNAI1hi, ZEB1medium | [67] |
| Human erlotinib-resistant NSCLC (HCC827) cells | Hybrid EMT, cell migration, spheroid formation | Cad-1+, Vimentin+, ZEB1hi | [68] |
| Human prostate cancer (PC-3/Mc) cells | Hybrid EMT, stemness | CD24+, CD44+ | [69] |
| Primary tumour- derived human prostate cancer (OPCT-1) cells | Co-expression of E/M phenotype | E-cad+, vimentin+, cytokeratin+, fibronectin+, N-cad+, SNAI1+, Slug+ | [70] |
| Human pancreatic cancer (PANC1 and MIAPACA2) cells | ↓E-Cad, ↑ZEB1, ↑vimentin | [71] | |
| Human NSCLC (A549, H460), primary NSCLC (LT73) cells |
↑CDH1, ↑SNAI2 | [92] | |
| In Vivo Studies | |||
| Genetic SCC mouse model | Hybrid EMT | Krt 14+, vimentin+ | [13] |
| Primary rhabdomyosarcoma NSTS-11 cells in NSG mice | Hybrid EMT, stemness | ↑(ZEB1, MME, LAMC2, or COL3A1), ↓(N-cad, SNAI1, FGF2, AOX1, or ANKRD1), ↑(KRT5, LAMA3, or ANK3), ↓(E-cad, P-cad, KRT14, KRT17, or KRT18) |
[72] |
| Primary human colorectal cancer PDXs in NOG mice | Hybrid EMT, metastasis |
E-cad+, ZEB1+ | [73] |
| Primary human ovarian cancer ocv316-X tumour xenograft in SCID-beige mice | Co-expression of E/M markers | E-cad+, Vimentin+ | [74] |
| KPCY mouse model of PDAC | β-catenin+, Claudin-7+, EpCAM+, E-cad+ | [76] | |
| Primary prostate cancer CPKV mice model | EpCAM+, Vimentin+ | [77] | |
| Prostate cancer DU145 subline in mouse xenografts | E-cad+, ZEB1+ | [78] | |
| Clinical Studies | |||
| Primary CRC tumour | Hybrid EMT | E-cad+, ZEB1+ | [73] |
| Metastatic tumour sites in prostate cancers patients | Co-expression of E/M markers | E-cad+, ZEB1+ | [78] |
| Primary HNSCC tumours | Hybrid EMT, metastasis |
↑Vimentin, ↑integrin α-5, ↑laminins, ↑MMPs | [93] |
| Primary prostate cancer cells | Co-expression of E/M markers | E-cad+, Vimentin+, Fibronectin+ | [82] |
| CTC from patients with metastatic NSCLC | Vimentin+, Krt+ | [83] | |
| CTCs from ovarian cancer patients | EpCAM+, CK5/7+, Muc-1+, N-cad+, Vimentin+, Snai+ | [84] | |
| CTCs from patients with metastatic CRPC | Hybrid EMT, stemness |
EpCAM+, Cytokeratins+, E-cad+, Vimentin+, N-cad+, O-cad+, CD133+ |
[85] |
| CTCs from women with metastatic BT | Hybrid EMT | Cytokeratins+, Vimentin+, N-cad+ | [85] |
| ESCC PT or MLN specimen from ESCC patients | E-cad+, N-cad+, vimentin+ | [86] | |
| CTC from early stage breast cancer patients | stemness | TWIST1+, CD44+, ALDH1+, EpCAM+ | [87] |
| Breast cancer samples from primary site and metastatic lymph nodes of breast cancer patients | Co-expression of E/M markers | E-cad+, vimentin+ | [88] |
| Human primary colorectal cancer specimen | Cytokeratin+, vimentin+ | [89] | |
| Primary HGSOC tumour | E-cad+, vimentin+ | [90] | |
| Primary AC, SCC tumours | Vimentin+/cytokeratin+, E-cad+/N-cad+ | [91] | |
Abbreviations: ANKRD1, ankyrin repeat domain-containing protein 1; AOX1, aldehyde oxidase 1; COL3A1, collagen Type III α1 Chain; FGF2, fibroblast growth factor; LAMC2, laminin subunit γ 2; MME, membrane metallo-endopeptidase.