TABLE 2.

The association between the overexpression of TLRs and the development of human cancers

	Up‐regulated TLRs	Outcome	References
Ovarian cancer	TLR4 TLR2‐TLR5	Recruits PI3K axis to increase XIAP leading to tumour growth and chemo‐resistance Inhibit apoptosis by increasing XIAP expression and Akt phosphorylation	33
Myeloma cells	TLR1, TLR7, TLR9	Prevent apoptosis through autocrine secretion of IL‐6 and induction of drug resistance	37
Breast cancer	TLR3, TLR4, TLR 9	Induce tumour metastasis through increasing of MMP13 and lipid peroxidation	70
Prostate cancer	TLR9	Induces metastasis through increasing MMP13 expression Enhancing cell survival and proliferation by activation of NF‐κB and c‐Myc	55
Melanoma	TLR2, TLR3, TLR4	Induce metastasis through increasing MMP13 Up‐regulation of pro‐inflammatory cytokines and chemokines, immunosuppressive cytokine	36, 56
Gastric cancer	TLR2, TLR9 TLR4, TLR5, TLR9 TLR2	Induce angiogenesis through elevation of COX‐2 and PGE2 expression Induce NF‐κB–dependent tumour invasion and metastasis Enhances tumour cells proliferation and survival through PI3K/Akt and NF‐κB axis	45, 60
Colorectal tumour	TLR4 TLR2	Induces angiogenesis through elevating COX‐2 and PGE2, as well as phosphorylation of EGFR Induces anti‐apoptotic effects through activation of PI3K/AKT and NF‐κB	61
HNSCC	TLR4 TLR3	Immune escape via secretion of IL‐6, IL‐8, VEGF and GM‐CSF and drug resistance Induces metabolic reprogramming by increasing HIF‐1α	69, 89
Colon cancer	TLR4	Apoptosis inhibition; relapse and metastasis	90
Pancreatic cancer	TLR2, TLR4, TLR9	Increase VEGF, PDGF, MAPK and pERK leading to inflammation and angiogenesis	91
Lung cancer	TLR2, TLR3, TLR4, TLR9 TLR4 TLR7, TLR8 TLR2	Resistance to TNF‐α or TRAIL‐induced apoptosis through NF‐κB up‐regulation Induces metastasis Increase the expression of Bcl‐2 by activating NF‐κB Increases tumour cells proliferation and IL‐8	34
Oral squamous cell carcinomas	TLR2 TLR3, TLR4 TLR4, TLR5	Up‐regulates the proliferative kinase ERK & reduce pro‐apoptotic caspase‐3 activity Induce metabolic reprogramming by increasing HIF‐1α Induce tumour invasion and metastasis	92
Bladder cancer	TLR2, TLR3, TLR4	Enhance transcription of genes involved in cell proliferation through activation of NK‐κB Induction of pro‐inflammatory and angiogenic factors such as COX‐2, VEGF and TGF‐β Conversion of M1 macrophage to M2	93
Hepatocellular carcinoma	TLR4 TLR2, TLR3, TLR6	Increases cell proliferation and survival through the NK‐κB and MAPK pathways Increases pro‐inflammatory factors like COX‐2 and prostaglandin through the STAT3 pathway Anti‐apoptotic effects by inhibition of caspase 3, 6, 7 and 9 transcription Increases tumour invasion and metastasis, especially macrovascular invasion Enhance cell proliferation and inflammation	94, 95
Oesophageal Cancer	TLR4 TLR3, TLR4, TLR7, TLR9	Immune escape and inflammation by up‐regulation of IL‐8 and COX‐2 Tumour metastasis via up‐regulation of p38 and selectin Enhance inflammation, invasion (especially lymph node metastasis) and proliferation	96
Adrenocortical carcinoma	TLR2, TLR4	Induction of inflammation via up‐regulation of TNF‐α, IL‐6 and IL‐8	97