Table 2 CAF-derived EV functions on cancer cell property

Proteins

From

To

CD81

Breast cancer

CAFs

Cancer cells

Enhance cancer motility and metastasis through activating Wnt-planar cell polarity (PCP) signalling pathway

[50]

Extracellular matrix proteins and ADAM10

Breast cancer

Induce aldehyde dehydrogenase expressionin cancer cells through Notch activation and enhance motility through the GTPase RhoA.

[115]

Wnt10b

Breast cancer

CAFs with low p85α expression transfer Wnt10b via EVs and promote cancer progression.

[116]

Amphiregulin

Colorectal cancer

TGF-β-induced CAF model secrete Amphiregulin via EVs and promote cell proliferation in EGF-dependent patient derived organoids

[118]

Wnt3a

Colorectal cancer

Expansion of cancer stem cell to enhance chemoresistance

[117]

Sonic Hedgehog (Shh)

Esophageal squamous cell carcinoma

Promote cancer cell proliferation. CAF-derived EVs may transfer Shh to enhance tumour growth.

[119]

Annexin A6

Gastric cancer

Activate FAK-YAP signalling through stavilizing integrin β1 to enhance drug resistance.

[120]

CD9

Gastric cancer

CAFs secrete CD-9 positive EVs and stimulate diffuse-type GC migration.

[51]

INHBA and THBS1/2

Gastric cancer

INHBA and THBS1/2 are associated with aggressive property of gastric cancer. HSF-1, master regulator of these molecules, may contribute to the loading of these molecules in MEF- and CAF-derived EVs.

[121]

Gremlin-1

Hepatocellular carcinoma

Promote EMT and sorafenib resistance via activating Wnt/β-catenin signalling pathway.

[200]

SLPI

Ovarian cancer

Promote cancer progression by activating PI3K and MAPK signalling pathways.

[194]

TGF-β1

Ovarian cancer

Promote EMT in cancer cells through inducing canonical TGF-β singalling.

[122]

Annexin A6

Pancreatic cancer

ANXA6- and CD9-double positive CAF-derived EVs facilitate p38 MAPK signal activation to enhance migratory ability in PDAC cells.

[52]

Galectin-1

Prostate cancer Pancreatic cancer Melanoma

CAF-derivved galectin-1 may contribute to cancer migration.

[123]

Coding RNAs

From

To

SNAI1 mRNA

Lung cancer

CAFs

Cancer cells

Transfer SNAI1 mRNA and promote EMT in cancer cells.

[124]

non-coding of transposable RNAs

From

To

LINC00355

Bladder cancer

CAFs

Cancer cells

Function as a sponge of miR-15a-5p and increase HMGA2 expression to promote cancer progression

[125]

LINC00355

Bladder cancer

Promote cancer cell proliferation.

[126]

Decreased miR-1-3p

Breast cancer

miR-1-3p expression is decreased in CAF-derived EVs. These CAF-derived EVs promote cancer progression. miR-1-3p targets GLIS1 expression in cancer cells.

[133]

Decreased miR-4516

Breast cancer

miR-4516 expression is decreased in CAF-derived EVs and also promote cancer progression. miR-4516targets FOSL1 to promote cancer progression.

[131]

Decreased miR-7641

Breast cancer

miR-7641 expression is decreased in CAF-derived EVs. These CAF-derived EVs can induce cancer stemness and metabolic reprogramming.

[132]

lncRNA SNHG3

Breast cancer

CAF-derived SNHG3 act as sponge for miR-330-5p expression to increase PKM protein expression results in metabolic reprogramming in cancer cells.

[62]

miR-16 and miR-148a

Breast cancer

FAK-null CAFs suppress cancer metastasis, and this CAF-derived EVs can partially contribute to the reduced tumour cell activities and metastasis.

[129]

miR-181d-5p

Breast cancer

Promote cancer cell migratrion and invasion through targeting CDX2 and HOXA5 to induce EMT in cancer cells.

[130]

miR-18b

Breast cancer

Promote cancer invasion and metastasis by targeting Transcription Elongation Factor A Like 7 (TCEAL7) expression in cancer cells.

[195]

miR-22

Breast cancer

CD63-positive CAF-derived EVs espress miR-22 and promote Tamoxifen resistance in cancer cells through targeting SFRS1 expression.

[58]

miR-3613-3p

Breast cancer

Promote cancer cell proliferation through targeting SOCS2 expression in cancer cells

[128]

miR-500a-5p

Breast cancer

Promote cancer proliferation and metastasis through targeting USP expression

[127]

miR-92

Breast cancer

Target directly the expression of LAT2 and induces PD-L1 expression through YAP activation in breast cancer cells.

[58]

Non-coding of transposable RNAs

Breast cancer

Stimulate RIG-I recognition to activate STAT1 in cancer cells.

[53]

miR-1323

Cervical cancer

Promote radioresistance via targeting PABPN1 and activating Wnt/β-catenin signalling pathway.

[198]

circN4BP2L2

Colorectal cancer

Promote cancer cell proliferation and metastasis. circN4BP2L2 in EVs targets miR-664b-3p to induce HMGB3 expression.

[188]

lncRNA CCAL

Colorectal cancer

Promotes Oxaliplatin resistance in CRC cells via stabilizing human antigen R (HuR) mRNA to increase β-catenin expression.

[56]

lncRNA H19

Colorectal cancer

Promote Cancer stemness and chemoresistance through targeting miR-141 expression and activating β-catenin signalling

[137]

lncRNA LINC00659

Colorectal cancer

Act as an RNA sponge for miR-342-3p expression to induce ANXA2 expression and promote EMT in cancer cells.

[142]

LncRNA SNHG3

Colorectal cancer

Promote cell proliferation via targeting miR-34b-5p to induce HOXC6 expression in cancer cell.

[196]

miR-135b-5p

Colorectal cancer

Promote tumour angiogenesis via targeting FOXO1 expression in cancer cell.

[189]

miR-135b-5p

Colorectal cancer

Might promote tumour angiogenesis and cancer cell proliferation via TXNIP expression.

[202]

miR-17-5p

Colorectal cancer

Promote cancer progression through targeting RUNX3 to activate MYC/TGF-β axis in cancer cells

[134]

miR-181-5p

Colorectal cancer

Promote 5-FU resistance via targeting neurocalcin δ　(NCALD) expression in colorectal cancer cells.

[193]

miR-21

Colorectal cancer

Promote liver metastasis via transfering miR-21 and influence cell proliferation and chemoresistance.

[138]

miR-224-5p

Colorectal cancer

Involve in cancer progression through targeting SLC4A4 expression.

[141]

miR-24

Colorectal cancer

Enhance methotrexate resistance of cancer cells via targeting CDX2 to regulate HEPH expression.

[139]

miR-590-3p

Colorectal cancer

Promote the radioresistance in cancer cells through targeting CLCA4 to activate PI3K/AKT signalling pathway and reduce expressions of cleaved-caspase 3 and cleaved-PRAP.

[140]

miR-92a-3p

Colorectal cancer

Promote cancer metastasis and chemotherapy resistance through targeting FBXW7 and MOAP1 expression

[136]

miR-93-5p

Colorectal cancer

Targeting FOXA1 and induce TGFB3b and promote radioresistance

[135]

Decreased miR-320a

Endometorial cancer

miR-320a expression is decreased in CAF-derived EVs and promote cancer progression. miR-320a target HIF1α expression in cancer cells.

[143]

Decreased miR-148b

Endometorial cancer

miR-148b expression is decreased in CAF-derived EVs to enhance cancer metastasis through inducing EMT. miR-148b in EVs may targeting DNMT1 expression.

[144]

lncRNA NEAT1

Endometorial cancer

Act as an RNA sponge for miR-26a/b-5p expression to induce YKL-40 expression via STAT3 signalling and enhance cancer progression.

[145]

LINC01410

Esophageal cancer

Promote EMT via targeting miR-122 and inducing PKM2 expression.

[199]

miR-21

Esophageal squamous cell carcinoma

CAF-derived miR-21 cooperates with IL-6 to induce monocytic myeloid-derived suppressor cells (M-MDSCs), resulting in cisplatin resistance regulation in cancer cells.

[146]

Decreased miR-34

Gastric cancer

miR-34 expression is decreased in CAF-derived EVs and promote cancer progression.

[147]

lncRNA circ_0088300

Gastric cancer

Act as an RNA sponge for miR-1305 expression to promote cancer progression. KHDRBS3 contributes to circ_0088300 transfer via CAF-derived Evs.

[150]

miR-199a-5p

Gastric cancer

Promote cancer progression by targeting FKBP5 expression and activating mTORC1 signalling in cancer cells.

[201]

miR-522

Gastric cancer

Suppress ferroptosis via targeting ALOX15 expressiion and promote chemoresistance. hnRNPA1 and USP7 are associated with miR-522 secretion via CAF-derived EVs.

[148]

MMP-11 and Decreased miR-139

Gastric Cancer

Transfer MMP-11 to promote cancer cell progression. miR-139 expression is decreased in CAF-derived EVs and also promote cancer progression. miR-139 may target MMP11.

[149]

Decreased miR-3188

Head and neck cancer

miR-3188 expression is decreased in CAF-derived EVs to promote cell proliferation and inhibit apoptosis in cancer cells. EV-derived miR-3188 targets BCL2 expression.

[151]

miR-196a

Head and neck cancer

Promote cisplatin resistance via targeting CDKN1B and ING5 expression.

[152]

Decreased miR-150-3p

Hepatocellular carcinoma

miR-150-3p expression is decreased in CAFs and their EVs to promote cancer cell progression.

[153]

Decreased miR-29b

Hepatocellular carcinoma

miR-29b expression is decreased in CAF-derived EVs and promote cancer migration and invasion. miR-29b may target DNMT3b to modulate EMT in cancer cells.

[154]

Decreased miR-320a

Hepatocellular carcinoma

miR-320a expression is decreased in CAF-derived EVs. These CAF-derived EVs promote cancer progression. miR-320a targets PBX1 expression in cancer cells.

[155]

Decreased let7a-5p

Lung cancer

Sulfonylurea receptor 1 (SUR1) expressing cancer cells decreased let-7a-5p expression in their EVs to induce CAFs. Mechanistically, let-7a-5p targets TGFBR1 to inactivate the TGF-β signalling in fibroblasts.

[184]

lncRNA OIP5-AS

Lung cancer

Export OIP-AS to suppress miR-142-5p and induce PD-L1 expression. EVs can be involved in immune tolerance of tumour.

[183]

LncRNA SNHG12

Lung cancer

Promote cisplatin resistance by binding to HuR to facilitate RNA stability and XIAP expression.

[187]

lncRNA TUG1

Lung cancer

Promote cancer cell migration, invasion, and glycolysis. TUG1 in EVs may target miR-524-5p to induce SIX1 expression.

[185]

miR-103a-3p

Lung cancer

Suppress apoptosis and promote cisplatin resistance through targeting Bak1 expression. Pum2 contributes to miR-103a loading into CAF-derived EVs.

[159]

miR-130a

Lung cancer

Cisplatin-induced miR-130a is transferred by CAF-derived EVs and promotes chemoresistance in cancer cells. PUM2 contributes to miR-130a packaging into CAF-derived EVs.

[158]

miR-20a

Lung cancer

Promote cancer cell proliferation and cisplatin resistance via targeting PTEN expression in non-small cell lung cancer cells.

[192]

miR-210

Lung cancer

Promote cancer cell migration and invasion through targeting UPF1 to induce EMT in cancer cells

[156]

miR-369

Lung cancer

Promote cancer cell migration and invasion through targeting NF1 and mediate MAPK signalling pathway

[157]

miR-4717-5p

Malignant lymphoma

Induce gemcitabine resistance through targeting ENT2 expression in cancer cells.

[55]

Decreased miR-34a

Oral squamous cell carcinoma

Promote cancer cell proliferation and metastasis through AKT/GSK-3β/β-catenin signalling. miR-34a can target AXL in cancer cells.

[161]

miR-382-5p

Oral squamous cell carcinoma

Promote cancer cell migration and invasion. miR-382-5p contributes to EV-mediated cancer progression.

[160]

miR-1228

Osteosarcoma

Promote cancer migration and invasion through targeting SCAI.

[162]

miR-21 isomiR

Ovarian cancer

Confer the chemo-resistance through targeting APAF1

[163]

miR-98-5p

Ovarian cancer

Promote cisplatin resistance via targeting CDKN1A.

[164]

miR-106b

Pancreatic cancer

Gemcitabine induce miR-106a in CAFs and their EVs. CAF-derived miR-106a can promote cancer cell proliferation.

[165]

miR-331-3p

Pancreatic cancer

Promote cancer progression via targeting SCARA5 expression in PDAC cells.

[191]

miR-92a-3p, miR-181a-5p, miR-222-3p, miR-221-3p, miR-21-5p

Pancreatic cancer

CAFs might transfer miRNAs in PDAC cells via EVs and promote gemcitabine resistance. miR-92a-3p could target PTEN expression in PDAC cells.

[190]

miR-1290

Prostate cancer

Promote EMT and metastasis via targeting GSK3β expression in cancer cell.

[197]

miR-146a-5p

Prostate cancer

Promote cancer metastasis. Treatment of Dihydrotestosterone (DHT) decrases miR-146a-5p in CAF-derived EVs and attenuate cancer promoting function.

[186]

miR-409

Prostate cancer

Promote epithelial-mesenchymal transition through repression of tumor suppressor genes such as Ras suppressor 1 and stromal antigen 2

[166]

miR-224-5p

Renall cell carcinoma

Contribute to cancer progression

[167]

Metabolites

From

To

mitochondorial DNA (mtDNA)

Breast cancer

CAFs

Cancer cells

Promote estrogen receptor-independent oxidative phosphorylation restore in cancer-stem like cells and increase self-renewal capacity in these cells.

[168]

Metabolites including amino acids and lipids

Prostate cancer

Affect the metabolic properties in prostate cancer cells

[60]

Others

From

To

RN7SL1

Breast cancer

CAFs

Cancer cells

Acting as damage-associated molecular patterns (DAMPs) and activating RIG-I in the recipient cancer cells

[54]

Protein binding, serine-type endopeptidase activity, signalling receptor and protein kinase binding-related molecules

Oral squamous cell carcinoma

CAF-derived EVs promote cancer invasion and apoptosis.

[169]

miR-146a and Snail mRNA

Pancreatic cancer

Gemcitabine induce the secretion of miR-146 and Snail mRNA via EVs and regulate survival and proliferation in cancer cells.

[170]