Receptors involved in immune cell stimulation and/or inhibition has not been fully tested. Here, we focused on signalling lymphocytic activation molecule MG132 Proteasome inhibitor family receptors. These receptors trigger both inhibitory and activation signals in immune cells. The SLAMF-R sub-family includes SLAMF1, SLAMF3, SLAMF5, SLAMF4, SLAMF6, and SLAMF7. The SLAMF-Rs are homophilic receptors that function as self-ligands. The SLAMF-Rs�� role in modulation of the immune response depends on SLAM-associated adapter molecules, EWS-FLI1�C activated transcript 2 and EAT-2-related transducer ). Another interesting feature of SLAMF-Rs relates to the presence of one or more immunoreceptor tyrosine-based switch motifs in their intracytoplasmic domains; the ITSMs recruit proteins from the signalling adaptor family, 
which includes SAP, EAT-2 and ERT. After binding, SAP adaptors couple the SLAMF-Rs to downstream signalling pathways. SLAMF3 is a transmembrane receptor whose expression has only been documented to date in thymocytes, T and B lymphocytes, dendritic cells, macrophages and NK cells. It has been shown that T cells from Ly9-knock-out mice proliferate poorly and produce less IL-2 after suboptimal stimulation with anti-CD3 in vitro. In fact, ectopic expression of SLAMF3 on non-hematopoietic B16 melanoma cells triggered their killing by NK cells via SLAMF3 homophilic interactions. On the basis of these observations, we sought to establish whether or not SLAMF molecules were expressed in liver tissue and to assess their involvement in hepatocyte proliferation and HCC. We first analysed the expression of SLAM molecules in hepatocytes and found that SLAMF3 was expressed by this cell type. We also observed a strong correlation between elevated SLAMF3 expression and low hepatocyte proliferation index suggesting that SLAMF3 homophilic interactions have a role in the mechanisms governing hepatocyte proliferation and the occurrence of HCC. In the present work, we showed for the first time that hepatocytes express SLAMF3 and provided evidence of the protein��s involvement in the progression of HCC. We also showed that mRNA and protein levels of SLAMF3 are significantly lower in HCC cell lines than in HHPHs. This difference was confirmed in tumour samples from HCC patients. The link between SLAMF3 expression and proliferation was demonstrated in vitro and then validated by the inhibition of HCC progression in Nude mice xenografted with SLAMF3-overexpressing HCC cells. It was recently reported that SLAMF3 has a similar role in lymphocytes; in contrast to SLAMF1 and SLAMF6, SLAMF3 has a negative effect on the signalling pathways required for innate-like lymphocyte development in the thymus. The observed effect may be attributed to both decrease in the proliferation of cells over-expressing SLAMF3 and the induction of apoptosis. In the present work, we also observed an association between restoration of SLAMF3 expression in HCC cells and the significant inhibition of ERK and JNK phosphorylation, which are constitutively activated in HCC and associated with the malignant HCC phenotype. Other studies using in vivo HCC animal models and human HCC tissue specimens have evidenced greater MAPK ERK expression and activity in tumours relative to the surrounding tissue. Indeed, ERK activity has clinical relevance since it positively correlated with tumour size and aggressive tumour behaviour and is considered to be an Nilotinib independent prognostic marker for poor overall survival. In human T cells, SLAMF3 engagement attenuates T-cell receptor signalling and reduces ERK activation. Murine T cells lacking SLAMF3 exhibit low Th2 responses. The JNK pathway is known to be a negative regulator of the p53 tumour suppressor and its role in cell survival is well established. Based on the correlation between elevated JNK kinase activity and tumour cell proliferation, it has been suggested that JNK has an oncogenic role. In contrast, reports of low p38 activity in HCC suggest that elevated p38 MAPK activity induces apoptosis in hepatoma cell lines. The members of the BCL2 family can function both as positive or negative regulators of apoptosis. Changes in BCL2 family expression and/or activation have been observed in several tumour types. Indeed, expression levels of BCLXL are elevated in HCC. Furthermore, a recent report indicated that BID is down-regulated in a subset of HCCs in the context of viral hepatitis. The pro-apoptotic BAD reportedly exert an important regulatory role in cell death in normal liver cells. Concordantly, BAD expression is low in HCC.