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| Pathway | Implication in cancer-related EMT | Roles in PCa | CTC analysis |
|
| AR | Opposing data: elevation of AR expression and AR signaling in prostate tumors promotes PCa metastasis by induction of EMT [39]; other data suggest AR reverses EMT and ADT can induce EMT [40, 41] | Cell proliferation and tumor progression [42, 43] | Different AR expression patterns, amplification, mutation, and variant expression in PCa CTC [44–47] |
| AKT | PI3K-AKT directly or in crosstalk with other signaling pathways can induce EMT [48, 49]. Drugs inhibiting EMT via the Akt/GSK-3β/Snail pathway decrease the invasiveness of PCa cells [50] | Implicated in PCa cell proliferation and resistance to apoptosis [51, 52] | Phosphorylated EGFR and PI3K/Akt signaling kinases detected in breast cancer patient CTCs [53], pERK/Akt pathway in CTCs in hepatocellular carcinoma patients [54], PTEN loss in circulating tumor cells in CRPC patients [55]. No report in PCa CTCs |
| Hippo | Deregulation of the Hippo pathway contributes to EMT in colorectal cancer [56], and FZD2 could promote clinically relevant EMT in hepatocellular carcinoma involving Hippo pathway [57] | Emerging roles in PCa development, progression, EMT, and mCRPC [58, 59] | TAZ expression detected in NSCLC CTCs [60], YAP association with metastasis in human gastric cancer [61]. No report in PCa CTCs |
| MAPK | MAPK mediates epithelial-mesenchymal transition in cooperation with TGF-β/Smad2 signaling and increased Snail and Twist expression [62–64] | Linked to proliferation, early relapse, and development of mCRPC [65, 66] | MAPK gene expression signature shown in pancreatic CTCs [67], detection of mutant RAS and RAF in CRC and in melanoma CTCs [68, 69]. No report in PCa CTCs |
| NF-κB | Hypoxia or overexpression of HIF-1α induces the EMT via NF-κB in pancreatic cancer cells [70] and inhibition of NF-κB deregulates EMT [71] | Promotes PCa cell survival, tumor invasion, metastasis, and chemoresistance [72, 73] | NSCLC-CTC gene expression profile was associated with cellular movement, cell adhesion and differentiation, and cell-to-cell signaling linked to PI3K/AKT, ERK1/2, and NF-κβ pathways [74]. No report in PCa CTCs |
| JAK/STAT | IFN-γ can induce epithelial-to-mesenchymal transition (EMT) in PCa cells via the JAK-STAT signaling pathway [75], and STAT3 may directly mediate EMT progression and regulate ZEB1 expression in CRC [76] | PCa progression, cell proliferation, and inhibition of apoptosis [51, 52] | No direct analysis of these pathways in CTCs |
| Wnt/β-catenin | Dysregulation of Wnt/β-catenin signaling has been implicated in the development of cancer in different tissues such as lung, skin, liver, and prostate [52], via regulating Zeb1 in CRC [77] | Wnt/β‐catenin pathway promotes the metastatic spread of prostate cancer cells by inducing EMT [78] | Epithelial type CTCs and activation of Wnt/β-catenin signaling in lung cancer cells [79]. No report in PCa CTCs |
| Notch | Crosstalk between the Jagged1/Notch and JAK/STAT3 signaling pathways by promoting EMT through Jagged-1 in ovarian cancer [80] | Notch signaling results in prostate tumor recurrence via EMT [81] | Increased production of ROS results in the upregulation of Notch1 in CTCs in metastatic breast and melanoma cancer [82]. No report in PCa CTCs |
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