Table 6.
Enzymes and Co-factors. This table describes intracellular proteins that may directly or indirectly participate in pathways required for EMP modulation by other enzymatic control of substrate proteins. Candidates that exhibit clinical correlation with lymph node metastasis are shown in bold.
| Cell Line | Target | EMT Regulation | KD/KO/Over-expression | Pathway/Mechanism | Functional Assay | Prognostic Association | EMT Activator | Reference |
|---|---|---|---|---|---|---|---|---|
| PANC-1 | USP22 | Positive, Direct | shRNA/Over-expression | USP22 expression correlated with Ezrin and FAK phosphorylation and EMT | Scratch wound, Transwell assays, WB | Not performed | - | [149] |
| 779E, 1334 PDCL | EIF5A | Positive, Indirect | shRNA/Over-expression | Mutant KRAS induces EIF5A, stimulating PEAK1 mediated ECM signaling. PEAK1 binds YAP/TAZ driving stem TFs | Sphere formation, IP, WB | Not performed | - | [150] |
| AsPC-1, PANC-1 | EIF4E | Negative, Indirect | siRNA | Knockdown of MNK effector, EIF4E, induced ZEB1 through repression of miR-200c, miR-141, MNK inhibitors induce MET | Collagen 3D, qPCR | Not performed | - | [94] |
| BxPC-3 | RGCC | Positive, Direct | siRNA | RGCC regulated by HIF1α and required for hypoxia induced EMT | qPCR, WB | Not performed | hypoxia | [151] |
| PANC-1 MIA PaCa-2 |
SET | Positive, Direct | shRNA/ Over-expression | SET over-expression activated Rac1/JNK/c-Jun pathway and decreased PP2A activity, N-cadherin and EMT TFs up | Transwell assays, Colony formation, Xenograft tumour growth and liver metastases | Not performed | - | [152] |
| MiaPaCa2, SW1990, PANC-1, CFPAC1 | GPX1 | Negative, Direct | shRNA/Over-expression | GPX1 IHC expression lower in PDAC, silencing induced EMT and gemcitabine resistance through ROS activated PI3K/Akt/GSK3B/SNAIL, Over-expression sensitized in vivo | Transwell migration, chemo-resistance, Xenografts, IHC of 281 PDAC tumours, and 42 paired PDAC v normal | Yes inversely prognostic by IHC | [153] | |
| BxPC-3, PANC-1, MiaPaCa2, PSN1 | HDAC1 | Positive, Indirect | siRNA | HDAC IHC expression and activity correlated with EMT phenotype | IHC, Transwell Invasion, IHC of 103 PDAC tumours | Survival by IHC | - | [154] |
| PANC-1 BxPC-3 |
Class I HDAC | Positive, Indirect | 4SC-202 small inhibitor | HDACi (inhibition) blocked TGFβ induced EMT in PANC-1, requiring BRD4 and MYC for effect of HDACi | Migration, sphere formation, Xenograft | Not performed | TGFβ (PANC-1) | [155] |
| CFPAC-1, L3.7-2 | PAFAH1B2 | Positive, Direct | siRNA/Over-expression | PAFAH1B2 IHC expression higher in PDAC, HIF1a expression regulated PAFAH1B2 via direct promoter binding | Transwell migration, Invasion, orthotopic Xenograft/ liver metastases, HIF1a/PAFAH1B2 co-localization in PDAC, IHC of 124 PDAC tumours and 70 normal | Survival by IHC and TCGA | hypoxia | [156] |
| PANC-1, MIAPaCa-2 | KDM4B | Positive, Direct | siRNA | KDM4B IHC expression correlated with ZEB1 in PDAC, knockdown inhibited TGFβ induced EMT in PANC-1 by regulating ZEB1 methylation | CHIP, scratch wound, Transwell assays, IHC of 49 PDAC tumours | Not performed | TGFβ | [157] |
| HPAC, BxPC-3, Colo357 PANC-1, MiaPaCa-2 | SMURF2 | Negative, Direct | SMURF negative regulator of TGFβ induced EMT, suppressed by miR-15b | Scratch wound, Transwell assays, WB | Not performed | TGFβ | [158] | |
| CAPAN-1 PANC-1 |
CUL4B | Positive, Direct | miRNA | CUL4B IHC expression higher in PDAC, regulated by miR -300, required for Wnt/β-catenin induced EMP | qPCR, Transwell assays, Xenograft, IHC of 110 PDAC v normal | Not performed | - | [159] |
| PANC-1 | KMT5C | Positive, Direct | siRNA | KMT5C (SUV420H2) expression higher in PanIN and PDAC, methylates H4K20me3,suppresses epithelial drivers FOXA1, OVOL2, OVOL2 | Transwell assays, chemo-resistance, sphere formation, | Not performed | - | [160] |
| PANC-1 | NOX4 | Positive, Direct | siRNA | NOX4 IHC expression elevated in PDAC, aids ROS generation and TGFβ induced EMT | Transwell assays, WB | Not performed | TGFβ | [161] |
| BxPC-3 | PAWR | Negative, Indirect | siRNA, Over-expression | PAWR (PAR4) suppressed in cisplatin resistant EMT cells, required PI3K/AKT signaling | Transwell assays, Proliferation, WB, Xenograft | Not performed | - | [162] |
| BxPC-3 | PPM1H | Negative, Indirect | siRNA | PPM1H expression decreased by TGFβ/BMP2 treatment, knockdown induced EMT | Proliferation, Transwell assays, WB, apoptosis | Not performed | TGFβ, BMP2 | [98] |
| PANC-1 | HMGN5 | Positive, Indirect | shRNA | HMNG5 silencing reduced Wnt expression | Xenograft, Transwell migration Invasion, WB, | Not performed | - | [163] |
| PANC-1 | GOLM1 | Positive, Direct | siRNA/ overexpression | GOLM1 (GP73) overexpression induced EMT and correlated with human metastasis and Xenograft growth | Xenograft, Transwell migration Invasion, Scratch wound, WB | Not performed | - | [164] |