Table 1.
Soluble and secreted factors that influence EMP. This table describes novel candidates that may be secreted within the ECM and act either directly through ligand-receptor interactions, or through mechanisms that remain to be demonstrated. Candidates that exhibit clinical correlation with lymph node metastasis are shown in bold.
| Cell Line | Target | EMT Regulation (Direct or Indirect Observation) | KD/KO/Over-expression | Pathway/Mechanism | Functional Assay | Human Prognostic Association | EMT Activator | Reference |
|---|---|---|---|---|---|---|---|---|
| BxPC-3 | DKK3 | Negative, Direct | Over-expression | DKK3 is overexpressed in tumour and is antagonist of WNT ligand activity, preventing nuclear translocation of β-catenin and EMP under hypoxia | Transwell assays, chemo-resistance, IHC in 75 matched PDAC v normal samples, xenograft growth | Not performed | Hypoxia | [111] |
| ASPC-1, PANC-1 | IGFBP2 | Positive, Direct | siRNA/Over-expression | IGFBP2 activated NF-κB through PI3K/AKT/IKK, inhibited by PTEN | WB, Transwell assays, orthotopic growth, IHC in 80 patient PDAC and lymph node samples | Survival and lymph node metastasis | - | [106] |
| PANC-1 | LTB4 | Positive, Direct | siRNA | LTB4 induced EMT through receptor BLT2 and ERK1/2 activation | WB, Transwell assays | Not performed | LTB4 | [112] |
| Patu8988, PANC-1 | DMKN | Positive, Indirect | shRNA | Knockdown reduced p-STAT3 and EMT increased ERK1/2, AKT | Proliferation, Transwell assays, Xenograft, IHC in 44 patient PDAC tumours | Correlated with T stage | - | [113] |
| PANC-1 | LGALS1 | Positive, Direct | shRNA/Over-expression | LGALS1 IHC expression correlated with MMP9 and Vimentin in PDAC. PSC LGALS1 promoted cancer cell EMT and activation of NF-κB | Xenograft, Proliferation, Invasion, IHC in 66 PDAC tumours | Not performed | [114] | |
| BxPC-3, CFPAC | SEMA3C | Positive, Indirect | shRNA/Over-expression | SEMA3C knockdown suppressed EMT and tumourigenesis, and activation of ERK1/2 signaling | Proliferation, migration, Scratch wound, Xenograft, IHC in 118 PDAC tumours | Stage, survival, recurrence | [115] | |
| Capan-1 | FUT3 | Positive, Direct | shRNA/Over-expression | FUT3 knockdown impeded proliferation, migration, tumour growth and TGFβ induced EMT | Proliferation, Scratch wound, Transwell assays, Xenograft | Not performed | TGFβ | [116] |
| PANC-1, MIAPaCa-2, Capan-2 | MIF/ NR3C2 | Positive, Indirect | siRNA/Over-expression | MIF induces miR-301b, targeting NR3C2, inducing EMT and chemo sensitivity | PDAC transcriptome by array, IHC of 173 PDAC, Proliferation, Colony formation, Transwell assays, chemo-resistance | NR3C2 inversely prognostic by RNA and IHC | - | [117] |
| PANC-1, BxPC-3 | WNT5A | Positive, Direct | siRNA, Over-expression | Wnt5a expression induced EMT and invasion and was elevated in PDAC by IHC | Scratch wound, Transwell assays, WB, orthotopic growth, IHC of 134 PDAC v normal | No | - | [118] |
| PANC-1 | LCN2 | Negative, Indirect | Over-expression | LCN2 expression correlated with better survival and lower EMT state | IHC of 60 PDAC tumours, Transwell assays | Protective by IHC | - | [119] |
| MIAPaca-2, BxPC-3, SUIT-2 | NOV | Positive, Indirect | shRNA/Over-expression | NOV expression high in PDAC by IHC, and induced EMT phenotypes in vitro/in vivo | Colony formation, soft agar, Proliferation, Transwell assays, in vivo metastasis | Not performed | - | [120] |
| PANC-1, BxPC-3 | CCL18 | Positive, Direct | CCL18 expressed in mesenchymal and cancer cells, and induced EMT | WB, Transwell assays, IHC of 62 PDAC tumours, serum ELISA from PDAC patients | Survival | - | [121] | |
| PANC-1, BxPC-3 | TUFT1 | Positive, Indirect | siRNA/Over-expression | TUFT1 expression correlated with T stage and lymph node metastasis by IHC, RNA expression correlated with HIF1a, SNAI1 and VIM | WB, Proliferation, scratch wound, Transwell assays, Xenograft, IHC of 63 PDAC tumours | Yes in TCGA by RNA | [122] | |
| SW1990, ASPC-1 | OLR1 | Positive, Direct | siRNA/Over-expression | OLR1 overexpressed in tumours and correlates with metastasis and poor survival, overexpression induced EMT | Transwell assays, scratch wound, Proliferation/apoptosis, IHC of 98 PDAC tumours | Yes survival by IHC and TCGA | - | [123] |
| MIAPaCa-2, PANC-1, ASPC-1, BxPC-3 | LOXL2 | Positive, Indirect | siRNA/Over-expression | LOXL2 IHC expression correlated with recurrence, depth of invasion and poor survival, and enhanced EMT in vitro | Transwell assays, IHC of 80 PDAC tumours | Yes by IHC | - | [124] |
| PANC-1, PK9 | TFF1 | Negative, Direct | siRNA | TFF only expressed in PanIN and intraductal neoplasia, not normal or invasive PDAC, knockdown activated EMT, loss of TFF in GEMM drove PanIN, PDAC and CAF infiltration | Transwell Invasion, Scratch wound, KC GEMM, IHC on small number of samples | Not performed | - | [125] |