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Table 1 Determinants of CSC and EMT in HCC

From: Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma

Molecular regulator

Signaling pathway

Study

Cell surface markers

 K19+

TGF-β-Smad

Kawai et al. [24]

 CD44+

ERK/Snail;

Gao et al. [78]

 

TGF-β/Smad; Akt/GSK-3β/β-catenin

Park et al. [79]

 CD133+

NF-kB

Liu et al. [26]

 CD90+

 

Yamashita et al. [45]

 EpCAM

 

Yamashita et al. [45]

 Vimentin+CD133-

 

Mitra et al. [70]

Transcription factors

 Nanog

Stat3/Snail

Yin et al. [25]; Yu et al. [80]

 Oct4

Stat3/Snail

Yin et al. [25]

 Slug

 

Sun et al. [69]

 Sox9

TGF-β/Wnt/β-catenin

Kawai et al. [82]

Oncogene

 Malestrom

Akt/GSK-3β/Snail

Liu et al. [81]

Microenvironmental cues

 Hepatic stellate cells

HGF/Met

Yu et al. [91]

 Tumor-associated macrophages

TGF-β1

Fan et al. [76]

 Artemin

 

Zhang et al. [83]

 Hypoxia

Akt

Zhang et al. [83]

Twist1/Bmi1

Liu et al. [92]

HIF-1α/Artemin/Akt

Zhang et al. [83]

Oxidative stress

 HCV infection

Ca2+ signaling

Iqbal et al. [94]

 Folate deficiency

miR-22

Su et al. [95]

Viral infection

 HCV geneotype 2A

Hypoxia/osteopontin/Akt/GSK-3β/β-catenin

Kwon et al. [84]

Iqbal et al. [94]

miRNA

 miR-200a

Wnt/β-catenin

Liu et al. [87]

 miR-125b

TGF-β/SMAD2/4

Zhou et al. [72]

 miR-148b

 

Liu et al. [88]

 miR-200b, miR-200c, miR-122, miR-145

DDX3

Li et al. [89]

Sphere formation

Notch

Li et al. [71]