title: Innate immunity and hepatocarcinoma: Can toll-like receptors open the door to oncogenesis?
abstract: Hepatocarcinoma (HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long ago. Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis. An effective innate immunity response relies on the toll-like receptors (TLR) found in several different liver cells which, through different ligands and many signaling pathways can elicit, not only a pro-inflammatory but also an oncogenic or anti-oncogenic response. Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets. We performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March 2015. TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNA-damages and to cell survival. However, pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis. TLR3 has a well-known protective role influencing crucial processes like angiogenesis, cell growth or proliferation. TLR4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed. TLR9's influence on carcinogenesis is also controversial and despite a potential anti-cancer capacity, a pro-tumorigenic role is more likely. Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported. As therapeutic targets, TLRs are already in use and have a great potential. In conclusion, TLRs have been shown to be an interesting influence on the HCC's microenvironment, with TLR3 clearly determining an anti-tumour influence. TLR4 and TLR9 are considered to have a positive relationship with tumour development even though, in each of them anti-tumorigenic signals have been described. TLR2 presents a more ambiguous role, possibly depending on the stage of the inflammation-HCC axis.
authors.affiliation: Jorge André Gomes Lopes, Marta Borges-Canha, Pedro Pimentel-Nunes, Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Jorge André Gomes
authors.initials: JA
authors.lastname: Lopes
authors.affiliation: Jorge André Gomes Lopes, Marta Borges-Canha, Pedro Pimentel-Nunes, Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Borges-Canha
authors.affiliation: Jorge André Gomes Lopes, Marta Borges-Canha, Pedro Pimentel-Nunes, Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Pimentel-Nunes
keywords: Carcinogenesis; Chronic inflammation; Hepatocarcinoma; Innate immunity; Toll-like receptor
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