Table 3 CAF-secreted factors and their roles in cancers

From: Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

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	^{219,449,450,451}
IL-6	GC, BLCA, GBC, BC, UCEC	Cancer cell	Promotes cancer progression	JAK/STAT3 pathway	^{230,448,452,453,454,455,456}
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	^{468,469,470,471,472}
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	^481,482,483
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	LC	Cancer cell	Promotes cell chemoresistance	HGF/IGF-1/ANXA2 pathway	⁴⁸⁹
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

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Table 3 CAF-secreted factors and their roles in cancers

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