Induction of c-Myc-dependent cell proliferation through toll-like receptor 3 in head and neck cancer

Pries, Ralph; Hogrefe, Lisa; Xie, Lei; Frenzel, H; Brocks, C.; Ditz, Claudia; Wollenberg, Barbara

doi:10.3892/ijmm.21.2.209

Cited by 37 publications

(44 citation statements)

References 20 publications

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“…Moreover, the induction of TLRs on tumor cells may directly promote proliferation, such as in human prostate cancer and in head and neck cancer. This reaction is time-and dose-dependent and is reflected by NF-κB induction and the subsequent upregulation of oncoprotein c-Myc [64,65]. However, there are studies suggesting a protective role of TLR stimulation and possible therapeutic options exploiting TLR ligation.…”

Section: The Results Of Tlr Activation -Tlrs In Carcinogenesismentioning

confidence: 99%

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

Wolska

Lech‐Marańda

Robak

2009

Cellular and Molecular Biology Letters

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Toll-like receptors (TLRs) have been described as major components of the innate immune system, recognizing the conserved molecular structures found in the large groups of pathogens called pathogen-associated molecular patterns (PAMPs). TLR expression is ubiquitous, from epithelial to immunocompetent cells. TLR ligation triggers several adapter proteins and downstream kinases, leading to the induction of key pro-inflammatory mediators but also anti-inflammatory and anti-tumor cytokines. The result of this activation goes beyond innate immunity to shape the adaptive responses against pathogens and tumor cells, and maintains host homeostasis via cell debris utilization. TLRs have already become potent targets in infectious disease treatment and vaccine therapy and in neoplastic disease treatment, due to their ability to enhance antigen presentation. However, some studies show the dual effect of TLR stimulation on malignant cells: they can be proapoptotic or promote survival under different conditions. It is therefore crucial to design further studies assessing the biology of these receptors in normal and transformed cells. The established role of TLRs in human disease therapy is based on TLR7 and TLR4 agonists, respectively for the novel treatment of some types of skin cancer and for the anti-hepatitis B virus vaccine. Some clinical trials involving TLR agonists as potent enhancers of the anti-tumor response in solid tumors have begun.

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Section: The Results Of Tlr Activation -Tlrs In Carcinogenesismentioning

confidence: 99%

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

Wolska

Lech‐Marańda

Robak

2009

Cellular and Molecular Biology Letters

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“…40 In addition, overexpression of TLR3 and c-Myc was reported to be induced by poly(I:C) treatment, which led to cell proliferation in head and neck cancer. 42 These reports indicate that the roles of TLR3 and c-Myc in innate immune system and their responses to poly(I:C) treatment might be type-specific for cancer. Nevertheless, our in vitro results demonstrate that TLR3 mRNA is upregulated by poly(I:C) treatment in AS cells and BE (2) Interestingly, we found that knockdown of TLR3 in AS cells can decrease c-Myc protein expression similar to poly(I:C) treatment, but which could not completely suppress the expression of poly(I:C)-induced p-IRF3.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of c-Myc is involved in TLR3-mediated tumor death of neuroblastoma xenografts

Lin

Huang

et al. 2016

Laboratory Investigation

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“…Indeed, TLR3 triggering induces apoptosis in breast cancer cells, melanoma cells, and renal cell carcinoma (19 -21). In contrast, proliferation increase and cytokine secretion are observed in lung cancer cells and in head and neck squamous cell carcinoma (22,23), prompting us to wonder whether this pathway is also functional in MM cells.…”

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confidence: 95%

TLR3 Ligand Induces NF-κB Activation and Various Fates of Multiple Myeloma Cells Depending on IFN-α Production

Chiron

Pellat‐Deceunynck

Amiot

et al. 2009

The Journal of Immunology

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Multiple myeloma (MM) cells express TLR. It has been shown that TLR ligands induce the proliferation, survival, and immune surveillance escape of MM cells through MyD88-TLR pathways. Deciphering TLR function in MM cells will help in understanding the mechanisms of tumor cell growth. In this study, we examined the response of MM cells to the MyD88-independent/TIR-domain-containing adapter-inducing IFN-β-dependent TLR3. Deregulation of NF-κB pathway is a feature of MM cells, and we wondered whether TLR3 activation could mobilize the NF-κB pathway. We show that five of seven human myeloma cell line (HMCL) cells expressed TLR3. In the presence of the synthetic TLR3 ligand (poly(I:C)), activation of NF-κB pathway was observed in three of five selected TLR3+ HMCL, NCI-H929, RPMI 8226, and KMM1. In agreement with NF-κB activation, only these three HMCL responded to poly(I:C), although by either an increase (KMM1) or a decrease (NCI-H929, RPMI 8226) of proliferation. We show that KMM1 increase of proliferation was prevented by NF-κB inhibitor. In contrast, inhibition of proliferation in both NCI-H929 and RPMI 8226 was due to IFN-α-induced apoptosis. We next demonstrated that p38 MAPK pathway controlled both IFN-α secretion and IFN-α-mediated cell death. Moreover, cell death also involved activation of ERK1/2 pathway. In conclusion, our results show that TLR3 ligand induces NF-κB pathway activation in MM and support a switching function of type I IFN in the functional outcome of TLR3 triggering in tumor cells.

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Induction of c-Myc-dependent cell proliferation through toll-like receptor 3 in head and neck cancer

Cited by 37 publications

References 20 publications

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

Toll-like receptors and their role in carcinogenesis and anti-tumor treatment

Downregulation of c-Myc is involved in TLR3-mediated tumor death of neuroblastoma xenografts

TLR3 Ligand Induces NF-κB Activation and Various Fates of Multiple Myeloma Cells Depending on IFN-α Production

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