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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