Constitutional loss of function (LOF) single nucleotide polymorphisms (SNPs) in pattern recognition receptors FPR1, TLR3, and TLR4 have previously been reported to predict oxaliplatin benefit in colorectal cancer.
Fusobacterium nucleatum-induced intestinal tumorigenesis can be inhibited by TAK-242, implicating TLR4 as a potential target for the prevention and therapy of F. nucleatum-related colorectal cancer.
Our study suggests that meat intake may activate TLRs at the epithelial surface, leading to CRC via inflammation by nuclear transcription factor-κB-initiated transcription of inflammatory genes, whereas intake of fiber may protect against CRC via TLR4-mediated secretion of interleukin-10 and cyclooxygenase-2.
For the first time, our results indicate an immunosuppressive effect of Fn by promoting M2 polarization of macrophages through a TLR4-dependent mechanism, which may serve as a promising target for immunotherapy of Fn-related CRC.
The aim of this study was to investigate TLR2 (-196 to-174del), TLR4 (Asp299Gly and Thr399Ile) and TLR9 (T1237C and T1486C) gene polymorphisms at risk of colorectal cancer (CRC) development and progression.
Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response.
It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer.
In this study, we investigated the underlying mechanism and role of Gal-1 in metastasis and invasion of colorectal cancer (CRC) cells after TLR4 stimulation.
TLR4 siRNA inhibits cell proliferation, migration and invasion by suppressing ACAT1 expression, suggesting that TLR4 may be a potential therapeutic target for the treatment of colorectal cancer.
Lipopolysaccharide increases the release of VEGF-C that enhances cell motility and promotes lymphangiogenesis and lymphatic metastasis through the TLR4- NF-κB/JNK pathways in colorectal cancer.
Homozygous carriage of the variant allele of the TLR4/rs5030728 polymorphism was associated with increased risk of CRC (incidence rate ratio (IRR) = 1.30; 95% confidence interval (CI): 1.05-1.60; P = 0.02 (gene-dose model); IRR = 1.24; 95%CI: 1.01-1.51; P = 0.04 (recessive model)).
Using a chemical-induced CRC model, increased epithelial apoptosis and decreased tumor multiplicity and sizes were observed in TLR4-mutant mice compared with wild-type (WT) mice with CD14(+)TLR4(+) colonocytes.
Using a primer extension method (SNaPshot), we genotyped two variants of TLR4D299G and T399I in 100 patients with colorectal cancer and 140 healthy controls in Tunisian population.
A subgroup analysis by ethnicity suggested that TLR-4 genetic polymorphisms were associated with an increased risk of CRC among Asians (allele model: OR = 1.50, 95%CI = 1.19 ∼ 1.88, P = 0.001; dominant model: OR = 1.49, 95%CI = 1.16 ∼ 1.92, P = 0.002; respectively), but not among Caucasians and Africans (all P>0.05).