Skip to main content

Table 1 Effects of CAFs-secreted factors on HCC

From: Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma

CAFs secretion

Molecules

Effect on HCC

Mechanism

References

ECM proteins

BMP4

Invasion

Trigger cytokines through SMAD pathway

[51]

COMP

Proliferation, migration, invasion,

Promote EMT process

[30]

MMP9

Invasion, metastasis

–

[53]

Growth factors

HGF

Proliferation

–

[54]

Stemness

Facilitate c-Met/ FRA1/ HEY1 signaling and STAT3 signaling

[55, 56]

TGF-β

Induce VM

VE-cadherin/MMP2/LAMC2 networks

[57]

VEGF

Angiogenesis

–

[58]

PDGF-C

Angiogenesis

–

[59]

PGF

Angiogenesis

–

[60]

Cytokines

CXCL12

Proliferation, migration, invasion

–

[49]

Induce VM

Activate VE-cadherin/ MMP2/LAMC2 network

[57]

Immunosuppression

Recruit monocytes and facilitate differentiation into MDSCs in IL-6-STAT3-dependent manner

[61]

IL-6

Proliferation, migration, invasion

Activate mTOR signaling

[62]

Immunosuppression

Activate STAT3 signaling

[61, 63, 64]

Stemness

IL-6/STAT3/notch signaling

[56, 65]

CCL2, CCL5

Migration

Hh pathway

[66]

CCL7, CXCL16

Migration, invasion

TGF-β signaling

[66]

FOXQ1

Initiation

Trans-activate NDRG1

[67]

Extracellular vesicles

Exsomal miR-320a

Suppress proliferation, migration

Inhibit the MAPK pathway

[68]

  1. BMP4, bone morphogenetic Protein-4; ECM, extracellular matrix; COMP, cartilage oligomeric matrix protein; MMP, metalloproteinases; EMT, epithelial–mesenchymal transition; HGF, hepatocyte growth factor; TGF-β, transforming growth factor-β; VM, vasculogenic mimicry; IL-6, interleukin 6; mTOR, mechanistic target of rapamycin kinase; STAT3, activate signal transducer and activator of Janus kinase; LAMC2, Laminin Subunit Gamma 2; VEGF, vascular endothelial growth factor; PDGF-C, platelet derive growth factor-C; PGF, placental growth factor; CCL2/5/7/12, chemokine (C–C motif) ligand 2/5/7/12; CXCL16, chemokine (C-X-C motif) ligand 16; MDSCs, marrow-derived suppressor cells; Hh, hedgehog; FOXQ1, forkhead box Q1; NDRG1, N-myc downstream-regulated gene 1; MAPK, mitogen-activated protein kinase