Sialidases or neuraminidases (NEU) are glycosidases which cleave terminal sialic acid residues from glycoproteins, glycolipids and oligosaccharides. Four types of mammalian sialidases, which are encoded by different genes, have been described with distinct substrate specificity and subcellular localization: NEU-1, NEU-2, NEU-3 and NEU-4. Among them, NEU-1 regulates many membrane receptors through desialylation which results in either the activation or inhibition of these receptors. At the plasma membrane, NEU-1 also associates with the elastin-binding protein and the carboxypeptidase protective protein/cathepsin A to form the elastin receptor complex. The activation of NEU-1 is required for elastogenesis and signal transduction through this receptor, and this is responsible for the biological effects that are mediated by the elastin-derived peptides (EDP) on obesity, insulin resistance and non-alcoholic fatty liver diseases. Furthermore, NEU-1 expression is upregulated in hepatocellular cancer at the mRNA and protein levels in patients, and this sialidase regulates the hepatocellular cancer cells’ proliferation and migration. The implication of NEU-1 in other cancer types has also been shown notably in the development of pancreatic carcinoma and breast cancer. Altogether, these data indicate that NEU-1 plays a key role not only in metabolic disorders, but also in the development of several cancers which make NEU-1 a pharmacological target of high potential in these physiopathological contexts.

Extracellular matrix components such as collagens are deposited within the tumor microenvironment at primary and metastatic sites and are recognized to be critical during tumor progression and metastasis development. This study aimed to evaluate the clinical and prognostic impact of Discoidin Domain Receptor 1 (DDR1) expression in colon cancers and its association with a particular molecular and/or morphological profile and to evaluate its potential role as a prognosis biomarker. Immunohistochemical expression of DDR1 was evaluated on 292 colonic adenocarcinomas. DDR1 was highly expressed in 240 (82.2%) adenocarcinomas. High DDR1 immunostaining score was significantly associated, on univariate analysis, with male sex, left tumor location, BRAF wild type status, KRAS mutated status, and Annexin A10 negativity. High DDR1 immunohistochemical expression was associated with shorter event free survival only. Laser capture microdissection analyses revealed that DDR1 mRNA expression was mainly attributable to adenocarcinoma compared to stromal cells. The impact of DDR1 expression on cell invasion was then evaluated by modified Boyden chamber assay using cell types with distinct mutational profiles. The invasion capacity of colon adenocarcinoma is supported by DDR1 expression. Thus, our results showed that DDR1 was highly expressed in most colon adenocarcinomas and appears as an indicator of worse event free survival.