Table 3.
CAF-secreted factors and their roles in cancers
| Factors | Cancer type | Recipient cell | Biological function | Activated pathway | Refs. |
|---|---|---|---|---|---|
| Cytokine | |||||
| IL-1β | OSCC | Cancer cell | Promotes cell growth | NF-κB pathway | 445 |
| IL-1β | OSCC, BC | Cancer cell | Promotes cell invasion | IL-1β/ IL-1R pathway | 446,447 |
| IL-6 | ESCA | Cancer cell | Promotes cell chemoresistance | STAT3/NF-κB pathway | 218,448 |
| IL-6 | LC, HCC, PRAD | Cancer cell | Promotes cell metastasis and chemoresistance | JAK2/STAT3 pathway | 219,449–451 |
| IL-6 | GC, BLCA, GBC, BC, UCEC | Cancer cell | Promotes cancer progression | JAK/STAT3 pathway | 230,448,452–456 |
| IL-6 | HNSC | Cancer cell | Promotes cancer progression | Integrin αvβ3/NF-κB pathway | 295 |
| IL-6 | CRC | Monocyte | Promotes cell adhesion | ERK1/2 pathway | 341 |
| IL-6 | HCC | Cancer cell | Promotes stem cell-like properties | STAT3/Notch pathway | 457 |
| IL-6 | HCC | Neutrophils | Regulates cell survival, activation, and function | STAT3/PD-L1 pathway | 458 |
| IL-8 | CRC | Monocyte | Recruits monocyte and promotes its polarization | IL-8/CXCR2 pathway | 341 |
| IL-8 | GC | Cancer cell | Promotes cisplatin resistance | NF-κB pathway | 459 |
| IL-11 | GC, LC | Cancer cell | Promotes cell chemoresistance and metastasis | JAK/STAT3 pathway | 174,460,461 |
| IL-17a | GC | Cancer cell | Promotes cell migration and invasion | JAK2/STAT3 pathway | 232 |
| IL-22 | GC | Cancer cell | Promotes cell invasion | STAT3 and ERK pathway | 462 |
| IL-23 | BC | Cancer cell | Promotes cell invasion and metastasis | p38/MAPK pathway | 178 |
| IL-25 | BC | Cancer cell | Suppresses cell metastasis | ND | 463 |
| IL-33 | HNSC | Cancer cell | Promotes cell migration and invasion | ND | 464 |
| Chemokine | |||||
| CXCL5 | CRC | Cancer cell | Promotes tumor immunosuppression | PI3K/AKT pathway | 465 |
| CXCL9 | OSCC | Cancer cell | Suppresses cell apoptosis | CXCL9/CXCR3 pathway | 466 |
| CXCL12 | CRC | Cancer cell | Promotes cell metastasis | PI3K/AKT pathway | 140 |
| CXCL12 | BC | Cancer cell | Promotes cell invasion | TGF-β pathway | 305 |
| CXCL12 | OC | Cancer cell | Promotes EMT and cisplatin resistance | Wnt/β-catenin pathway | 467 |
| CXCL12 |
LC, HNSC, PAAD, GC |
Cancer cell | Promotes cancer progression | CXCL12/CXCR4 pathway | 468–472 |
| CCL3 | PRAD | Cancer cell | Promotes cell migration and invasion | JAK/STAT3 pathway | 473 |
| CCL5 | GC | Cancer cell | Promotes cell progression | CCL5/CCR5 pathway | 474 |
| CXCL2 | LUAD | Cancer cell | Promotes cancer immunosuppression | ND | 475 |
| CXCL16 | BC | Monocyte | Promotes the recruitment of monocyte | ND | 476 |
| SDF-1 | PAAD, CRC | Cancer cell | Promotes cell gemcitabine resistance and metastasis | SDF-1/CXCR4 pathway | 477,478 |
| SDF-1 | UCEC | Cancer cell | Promotes cancer progression | PI3K/AKT and MAPK/ERK pathway | 479 |
| Growth factors | |||||
| CRC | Cancer cell | Promotes cell cetuximab resistance | MAPK pathway | 253 | |
| FGF1 | OC | Cancer cell | Promotes cancer progression | FGF/FGFR pathway | 480 |
| FGF2 | BC, LC, CRC | Cancer cell | Promotes cancer progression | FGF/FGFR pathway | 481–483 |
| FGF9 | GC | Cancer cell | Promotes cell invasion | ERK and AKT pathway | 484 |
| GPER | BC | Cancer cell | Promotes cell proliferation | GPER/EGFR/ERK pathway | 248 |
| GDF15 | PRAD | Cancer cell | Promotes cancer progression | TGF-β/GDF15 pathway | 485 |
| HGF | CRC, GC, HNSC | Cancer cell | Promotes cell progression and metastasis | HGF/c-Met pathway | 143,452,486 |
| HGF | GC | HUVEC | Promotes angiogenesis | PI3K/AKT and ERK1/2 pathway | 147 |
| HGF | HCC | Cancer cell | Promotes cell chemoresistance | MEK-ERK1/2 pathway | 487 |
| HGF | HCC | Cancer cell | Promotes cell plasticity | c-Met/FRA1/HEY1 pathway | 488 |
| HGF | LC | Cancer cell | Promotes cell chemoresistance | HGF/IGF-1/ANXA2 pathway | 489 |
| IGF-1 | |||||
| IGF-1 | BLCA | Cancer cell | Promotes cell chemoresistance | IGF-1/AKT pathway | 355 |
| IGF-1 | CRC | Cancer cell | Promotes cell survival | IGF-1/IGF1R pathway | 490 |
| IGF-2 | AC | Cancer cell | Promotes cell growth | PI3K/AKT/mTOR pathway | 142 |
| IGF-2 | LC | Cancer cell | Promotes cell chemoresistance | IGF-2/IGF‐1R pathway | 491 |
| TGF-β1 | BC, PRAD | Cancer cell | Promotes cell proliferation and migration | TGF-β/Smad pathway | 492,493 |
| VCAM-1 | LC | Cancer cell | Promotes cell growth and invasion | AKT and MAPK pathway | 138 |
| VCAM-1 | GC | Cancer cell | Promotes cell invasion | JAK/STAT1 pathway | 494 |
| Others | |||||
| ADAM17 | BC | Cancer cell | Promotes cell proliferation | EGFR, AKT, and ERK pathway | 495 |
| Activin A | CRC | Cancer cell | Promotes cell migration and invasion | ND | 496 |
| ANXA3 | LC | Cancer cell | Promotes cell cisplatin resistance | ANXA3/JNK pathway | 497 |
| Asporin | GC | CAF | Promotes CAF migration | ND | 498 |
| CD9, GAS6 | GC | Cancer cell | Promotes cell migration | ND | 499,500 |
| CDH-11 | BC | Cancer cell | Promotes cell migration | ND | 501 |
| CLEC3B | CRC | Cancer cell | Promotes cell migration | ND | 502 |
| Collagen | BC | Cancer cell | Promotes cell chemoresistance | PI3K/AKT pathway | 503 |
| Collagen | PDAC | Cancer cell | Promotes cell growth and migration | Integrin β1/FAK pathway | 504 |
| Fatty acids | CRC | Cancer cell | Promotes cell migration | ND | 505 |
| FN | PRAD | Cancer cell | Promotes cell migration | ND | 313 |
| Gal1 | GC | Cancer cell | Promotes cancer progression and metastasis | ND | 506 |
| Galectin-1 | GC | HUVEC | Promotes angiogenesis | ND | 507 |
| Grem1 | BC | Cancer cell | Promotes cancer progression | BMP/Smad pathway | 508 |
| HIAR | BC | Endothelial cell | Promotes angiogenesis and cell migration | VEGF/VEGFR pathway | 509 |
| HIC-5 | ESCA | Cancer cell | Promotes cell metastasis | ND | 510 |
| HMGB1 | BC | Cancer cell | Promotes cell stemness and tumourigenicity | HMGB1/TLR4 pathway | 511 |
| Lactate | BC | Cancer cell | Promotes cell invasion | TGF-β1/p38/MAPK pathway | 512 |
| LOX | GC | Cancer cell | Promotes cell growth | ND | 513 |
| LOXL2 | CRC | Cancer cell | Promotes cell invasion and metastasis | FAK pathway | 514 |
| Lumican | GC | Cancer cell | Promotes cell tumorigenesis and metastasis | Integrin β1/FAK pathway | 515 |
| M-CSF | PDAC | Monocyte | Promotes TAM phenotype | ND | 516 |
| MFAP5 | OSCC | Cancer cell | Promotes cell proliferation and migration | MAPK and AKT pathway | 517 |
| MK | OSCC | Cancer cell | Promotes cell cisplatin resistance | ND | 518 |
| MMP2 | CESC, OSCC | ECM | Promotes cancer invasion | ND | 519,520 |
| NAB2 | HNSC | Cancer cell | Promotes cell growth | ND | 521 |
| Notch3 | HCC | Cancer cell | Promotes cell self-renewal | ND | 522 |
| PAI-1 | ESCA | Cancer cell | Promotes cell cisplatin resistance | AKT and ERK1/2 pathway | 523 |
| POSTN | GC | Cancer cell | Promotes cell growth | ERK pathway | 177 |
| POSTN | HNSC | Cancer cell | Promotes cell stemness | PTK7-Wnt/β-catenin pathway | 190 |
| POSTN | CESC | Endothelial cell | Promotes cancer metastasis | FAK/SRC pathway | 524 |
| POSTN | OC, OAC | Cancer cell | Promotes cell cisplatin resistance and invasion | PI3K/AKT pathway | 525,526 |
| Pyruvate | Lymphoma | Cancer cell | Promotes cell survival | ND | 361 |
| RANKL | OSCC | Osteoclast | Promotes bone invasion | ND | 527 |
| SNAI1 | LC | Cancer cell | Promotes cell migration and invasion | ND | 528 |
| TNFSF4 | LUAD | Cancer cell | Promotes chemoresistance | NF-κB/BCL-XL pathway | 529 |
| uPA | ESCA | Cancer cell | Promotes cancer progression | PI3K/AKT and ERK pathway | 175 |
| WNT2 | CRC | Cancer cell | Promotes cell invasion and migration | ND | 205,206 |
AC anal cancer, ANXA3 annexin A3, BC breast cancer, BLCA bladder cancer, CAF cancer-associated fibroblast, CDH-11 cadherin-11, CESC cervical and endocervical cancer, CLEC3B c-type lectin domain family 3 member B, CRC colon adenocarcinoma, ECM extracellular matrix, EGF epidermal growth factor, EGFR epidermal growth factor receptor, ERK extracellular regulated protein kinases, ESCA esophageal carcinoma, FGF fibroblast growth factor, FN fibronectin, Gal1 galectin-1, GAS6 growth arrest specific protein 6, GBC gallbladder cancer, GC gastric cancer, GDF15 growth differentiation factor 15, GPER estrogen receptor, Grem1 gremlin 1, HCC hepatocellular carcinoma, HGF sepatocyte growth factor, HIAR hypoxia-induced angiogenesis regulator, HIC-5 hydrogen peroxide-inducible clone 5, HMGB1 high-mobility group box 1, HNSCC head and neck squamous cell carcinoma, HUVEC human umbilical vein endothelial cell, IGF insulin-like growth factor, IL interleukin, JAK janus tyrosine kinase, LC lung cancer,LOX lysyl oxidase, LOXL2 lysyl oxidase-like 2, LUAD lung adenocarcinoma, MAPK mitogen-activated protein kinase, MEK mitogen-activated protein kinase, MFAP5 microfibril associated protein 5, MK midkine, mTOR mammalian target of rapamycin, ND not determined, NF-κB nuclear factor kappa-B, OAC esophageal adenocarcinoma, OC oarian cancer, OSCC oral squamous cell carcinoma, PAAD pancreatic adenocarcinoma, PDAC pancreatic ductal adenocarcinoma, PAI-1 plasminogen activator inhibitor 1, PD-L1 programmed cell death 1 ligand 1, PI3K PI3 kinase, POSTN periostin, PRAD prostate adenocarcinoma, PTK tyrosine protein kinase, RANKL receptor activator of nuclear factor kappa-B ligand, SDF-1 stromal cell-derived factor-1, SPARC secreted protein acidic and rich in cysteine, STAT3 signal transducer and activator of transcription 3, TGF transforming growth factor, TNFSF4 tumor necrosis factor ligand superfamily member 4, UCEC uterine corpus endometrial carcinoma, VCAM-1 vascular cell adhesion molecule-1