Table 1 EMT markers, cancer stem cell markers and signaling pathways involved in EMT and CSC in prostate cancer, especially in castration-resistant prostate cancer

E-cadherin

Regulates the invasive capacity of prostate cancer cells

[3, 57, 58]

β-Catenin

Regulates the process of EMT and metastatic phenotypes

[59]

N-cadherin

Promotes growth, metastasis and castration resistance in prostate cancer

Yes

[12, 60, 61]

Cadherin-11

Enhances migration and invasion capacity of prostate cancer cells, increases the association with osteoblasts

[14, 62]

Vimentin

Promotes prostate cancer cell invasion and metastasis

Yes

[63]

Fibronectin

Protects cells from undergoing apoptosis

[64, 65]

Collagen 1

Have an effect on EMT of prostate cancer cells

[65]

alphaII(b)beta3 integrin

Participates in the metastatic progression of prostatic adenocarcinoma

[66]

Syndecan-1

Associates with Gleason score and tumor progression of prostate cancer

[67–69]

Zeb1

Altering the invasive phenotype of Prostate cancer cells

Yes

[2, 8, 70]

Slug

Correlates with advanced pathological grades of prostate cancer

Yes

[11, 71]

Snail

Contributes to prostate cancer progression and metastasis

[4, 5, 72, 73]

Twist

Correlates with Gleason grading and metastasis

Yes

[9, 10]

ETS-1

Mediates by TGF-β, affects cell growth and tumor formation

Yes

[74, 75]

CSC markers

Function

CRPC

Refs

Lgr4

Regulates early prostate development and stem cell differentiation

[32]

α2β1 integrin

Produces prostate-like glands

[30]

CD133

Functions as a normal prostate stem cell marker and has tumor formation ability

[76]

CD166

A potential surface marker for castration resistant tumor cells

Yes

[21]

PSA

Displays increased colony and sphere-form capacity

Yes

[22]

CD44

Associates with cells of neuro-endocrine phenotype

[77]

CD44⁺/α2β1^hi/CD133⁺

Presents high proliferative ability in vitro and can differentiate to an AR–positive phenotype similar to prostate cancers in vivo

[78]

CD44+ CD24(-)

Exhibits stem cell characteristics and predicts overall survival in prostate cancer patients.

[79]

Sca-1

Have high proliferative ability and high capacity to reconstitute prostatic tissue

[31]

Nkx3.1

Indicates that luminal cells might be a cell of origin

Yes

[20]

p63

Produces all epithelial lineages of the adult prostate (i.e., basal, luminal, and neuroendocrine cells)

[80, 81]

Lin^-Sca-1^-CD49f⁺ (LSC)

Produces prostatic tubule structures

[82]

Lin^-CD44⁺CD133⁺Sca-1⁺CD117⁺

Produces a prostate after transplantation in vivo

[29]

Trop2

Trop2^hi basal cells give rise to basal, luminal, and neuroendocrine cells in vivo

[83]

ALDH1

Associates with a poor prognosis for patients with prostate cancer

[84, 85]

Nanog

Promotes CSC phenotypes and properties in vitro and in vivo, promotes AI phenotypes and CRPC regeneration

Yes

[24, 25]

Bmi-1

A key regulator of self-renewal activity, plays central roles in malignant progression of prostate cancer

Yes

[26]

Sox2

Inhibits by AR signaling and play an important role in CRPC

Yes

[28]

TRA-1-60, CD151 and CD166

Exhibits enhanced sphere-forming capacities in vitro and tumor-initiation capacities in vivo

[86]

Signal pathway involved CSC and EMT

Function

CRPC

Refs

AR

A key regulator for the acquisition of EMT phenotypes

Yes

[42, 45]

PTEN/AKT

Promotes prostate tumor growth and metastasis

[87]

AKT/GSK-3β

Participates in TNFα-induced EMT process

[88]

ERK

Has a profound feedback on EGFR signaling

[89]

AKT

Has a great effect on cell migration via induction of the EMT characteristics

[89]

TGF-β

Associates with malignant progression of prostate cancer by activation of the EMT phenotypes

[90, 91]

CCL2/CCR2-STAT3

Promotes prostate cancer cell migration/invasion and EMT pathways

Yes

[92]

Hsp27-STAT3-Twist

Promotes prostate cancer metastasis, regulates the process of EMT

Yes

[39]

PTEN and RAS/MAPK

Accelerates prostate cancer malignant progression accompanied by acquisition of EMT phenotypes and stem-cell like properties

Yes

[37]

NF-kappaB

Correlates with EMT in human prostate cancer cells and may be functionally associated with the stem-like human prostate tumor initiation cells

[86, 93, 94]

JAK-STAT

Participates in significantly different gene expression in prostate cancer stem cells

[95]

PDGF-D

Mediates EMT process and regulates cancer cell invasion

[96]

IGF-1

Regulates EMT associated migration and invasion via elevated Zeb1 expression

Yes

[8]

FGFR-1

Leads to an EMT and distant metastasis

[38]

EGFR

Presents loss of cell-cell junctions with decreased epithelial markers and enhanced mesenchymal markers

[89]

WNT

Mediates EMT phenotypes and stemness maintenance of prostate cancer cells

Yes

[40, 97]

Notch and Hedgehog

Regulates drug resistance and plays important roles in malignant transformation

Yes

[98, 99]

Hypoxia-ERβ-HIF-1a/VEGF-A

Mediates EMT and have an implication in Gleason grading

[100]

DAB2IP

Regulates EMT and prostate cancer metastasis and serves as a target gene of EZH2 in prostatic epithelium

[101–103]

p63/miR205

Suppresses cell migration and metastasis

[104]

Produces changes in Golgi polarization