Toll-Like Receptor-4 Promotes the Development of Colitis-Associated Colorectal Tumors

Fukata, Masayuki; Chen, Anli; Vamadevan, Arunan S.; Cohen, Jason; Breglio, Keith J.; Krishnareddy, Suneeta; Hsu, David S.; Xu, Ruliang; Harpaz, Noam; Dannenberg, Andrew J.; Subbaramaiah, Kotha; Cooper, Harry S.; Itzkowitz, Steven H.; Abreu, María T.

doi:10.1053/j.gastro.2007.09.008

Cited by 558 publications

(533 citation statements)

References 40 publications

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“…Also, studies of colitis-associated neoplasia in humans show COX-2 overexpression in neoplastic lesions (1). Furthermore, in an animal model of colitis-associated cancer, increased mucosal EGFR phosphorylation and COX-2 expression have been reported (21). This correlation between EGFR phosphorylation and increased COX-2 expression in an inflammatory environment is certainly consistent with our results, and it may define a mechanism that explains the different outcomes of tissue toward ulceration or neoplasia.…”

Section: Discussionsupporting

confidence: 89%

TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells

Hobbs¹,

Goettel

Liang³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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TNF and epidermal growth factor (EGF) are well-known stimuli of cyclooxygenase (COX)-2 expression, and TNF stimulates transactivation of EGF receptor (EGFR) signaling to promote survival in colon epithelial cells. We hypothesized that COX-2 induction and cell survival signaling downstream of TNF are mediated by EGFR transactivation. TNF treatment was more cytotoxic to COX-2−/−mouse colon epithelial (MCE) cells than wild-type (WT) young adult mouse colon (YAMC) epithelial cells or COX-1−/−cells. TNF also induced COX-2 protein and mRNA expression in YAMC cells, but blockade of EGFR kinase activity or expression inhibited COX-2 upregulation. TNF-induced COX-2 expression was reduced and absent in EGFR−/−and TNF receptor-1 (TNFR1) knockout MCE cells, respectively, but was restored upon expression of the WT receptors. Inhibition of mediators of EGFR transactivation, Src family kinases and p38 MAPK, blocked TNF-induced COX-2 protein and mRNA expression. Finally, TNF injection increased COX-2 expression in colon epithelium of WT, but not kinase-defective EGFRwa2and EGFRwa5, mice. These data indicate that TNFR1-dependent transactivation of EGFR through a p38- and/or an Src-dependent mechanism stimulates COX-2 expression to promote cell survival. This highlights an EGFR-dependent cell signaling pathway and response that may be significant in colitis-associated carcinoma.

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Section: Discussionsupporting

confidence: 89%

TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells

Hobbs¹,

Goettel

Liang³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It was demonstrated that inflammation-associated genes, such as COX-2, NOS-2, and IFN-inducible gene 1-8U, are up-regulated in inflamed mucosal areas and in CRC. Studies have also shown that activation of TLR4 enhances COX-2 expression and that increasing epidermal growth factor receptor signaling promotes CRC development [54]. Inflammation-associated cytokines, such as IL-6, IL-23, and TNF-a, also contribute to the development and growth of colitis-associated CRC.…”

Section: Ibd and Cancermentioning

confidence: 99%

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Libreros

Iragavarapu-Charyulu

2015

Journal of Leukocyte Biology

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Inflammation plays a vital role at different stages of tumor progression. The development of tumors is affected by inflammatory mediators produced by the tumor and the host. YKL-40/chitinase-3-like-1 protein is often upregulated in inflammation-associated diseases. With the use of chronic inflammatory disease systems, we describe the role of YKL-40/chitinase-3-like-1 protein in enhancing the inflammatory response and its implications in tumorigenesis. We also discuss how pre-existing inflammation enhances tumor growth and metastasis. In this mini-review, we highlight the effect of YKL-40/ chitinase-3-like-1 protein-associated inflammation in promoting tumor progression. J. Leukoc. Biol. 98: 931-936;

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“…S2). In AOM/DSS model, the tumor cells derive from IECs, IECs express a variety of TLRs, 15 which are activated under inflammatory condition. Previous study has demonstrated that TLRs on IECs serve as more important pro-inflammatory factors in AOM/DSS-induced CAC model.…”

Section: Wsx-1 Deficiency Leads To Higher Level Of Inflammatory Cytokmentioning

confidence: 99%

“…14 Previously study reported that mice in the absent of TLR4 are protected from AOM/DSS-induced inflammation-associated tumorigenesis. 15 By generating the bone marrow chimera, the same research group demonstrated that rather than haematopoietic cells, increased TLR4 signaling in IECs is more responsible for higher risk of inflammation-associated neoplasia. 16 Interleukin 27 (IL-27) is a heterodimeric cytokine combined with p28 and Epstein-Barr virus-induced gene (EBI3).…”

Section: Introductionmentioning

confidence: 99%

Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells

et al. 2017

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Toll-Like Receptor-4 Promotes the Development of Colitis-Associated Colorectal Tumors

Cited by 558 publications

References 40 publications

TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells

TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cells

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Protective function of interleukin 27 in colitis-associated cancer via suppression of inflammatory cytokines in intestinal epithelial cells

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