Table 1.
Tumour cell’s secreted factors and their functions over CAFs.
| Factors | Mode of Action | References |
|---|---|---|
| Cytokines | CAF activation/inactivation | [4,22,23,24,32,33,34,35,36,37,38,39,40,41,42,43,44,45] |
| IL-1 | CAF activation: Promotes cell growth and invasion by NF-κB and IL-1β/IL-1R pathway | [8,45,46,47] |
| TGF-beta | CAF activation: Promotes cell proliferation and migration by TGF-β/Smad pathway | [22,37,38,39,40,41,42,48,49,50,51,52,53,54,55,56,57,58,59,60,61] |
| IL-6 | CAF activation: Promotes cell chemoresistance, cancer progression, cell metastasis and chemoresistance and cell adhesion by STAT3/NF-kbeta, JAK2/STAT3, ERK1/2, STAT3/Notch, and STAT3/PD-L1 pathways | [23,24,36,39,46,50,59,62,63,64] |
| PDGF | CAF activation | [39,40,48,49,65,66,67,68,69,70,71,72,73,74,75,76,77,78] |
| EGF | CAF activation | [49,79,80,81] |
| IGF | CAF activation: Promotes cell chemoresistance, cell survival, and cell growth by IGF-/AKT, IGF/IGFR, and PI3K/AKT/mTOR pathways | [49,82,83,84,85] |
| JAK2/STAT3 | CAF activation | [40,86] |
| YAP1/TEAS1 | CAF activation | [87,88] |
| p53 | CAF inactivation | [89] |
| VEGF | CAF activation | [51,75,76,90,91] |
| CXCL12 | CAF activation: Promotes cell metastasis, cell invasion, EMT and cisplatin resistance and cancer progression by PI3K/AKT, TGF-β, Wnt/β-catenin, and CXCL12/CXCR4 pathways | [32,33,34,35,70,83,92,93,94,95,96,97,98,99] |
| TIMP-1 | CAF inactivation | [100,101,102,103] |
| OPN | CAF activation | [44,53,79,104,105,106,107,108,109,110] |
| MAPK | CAF activation | [44] |
| AKT | CAF activation | [44,98] |
| ERK1/2 | CAF activation | [109,110] |
| c-Ski | CAF inactivation | [111] |
| IL-33 | CAF activation: Promotes cell migration and invasion | [112] |
| TNF | CAF activation | [113] |
| SHH | CAF activation | [114] |
| miRNAs | CAF activation/inactivation | [115,116,117,118,119] |
| miR-200s | CAF activation: Invasion, metastasis via transcription factors Fli-1 and TCF12 | [70] |
| miR-21 | CAF activation: miR-21 and Smad7 induce CAF by TGF-β1 signalling regulation. Motility and invasion by MMP inhibitor RECK |
[120,121] |
| miR-155-5p | CAF activation: Angiogenesis by SOCS1/JAK2/STAT3 signalling pathway | [122] |
| miR-1247-3p | CAF activation: Stemness, EMT, chemoresistance, and tumorigenicity by IL-6/8; lung metastasis by β1-integrin-NF-κB pathway | [123] |
| miR-211 | CAF activation | [124] |
| lncRNA | CAF activation/inactivation | [125,126,127] |
| LPA | CAF activation | [128] |
| GPE | CAF activation: Promotes cell proliferation by GPER/EGFR/ERK pathway | [129] |
| DAPT | CAF inactivation | [130] |
| Tumour-derived exosome | CAF activation | [131] |
| Mitocondrial transfer | CAF activation | [132] |
| SMAD | CAF activation/inactivation | [121,127,133,134] |
| Smad2/3 | CAF activation | [134,135] |
| Smad4 | CAF activation | [127,133,134] |
| Smad7 | CAF inactivation | [121] |
Green stands for CAFs’ activators factors; red for CAFs’ inactivators factors; and yellow for factors with dual function (activators and inactivators).