Soluble E-cadherin is a 80 kDa protein fragment coming from the proteolytic cleavage of the extracellular domain of the full length epithelial cadherin, a molecule involved in cell adhesion/polarity and tissue morphogenesis. In comparison with normal epithelia, cancer cells show a decreased cadherin-mediated intercellular adhesion, and sE-cad levels normally increase in body fluids (blood and urine). This review focuses on soluble E-cadherin in sera of patients affected by three solid cancers (breast, gastric, and colorectal cancers) and how its levels correlate or not with some cancer parameters (e.g., dimension, progression, and localisation). We will describe the main proteomics approaches adopted to measure sE-cad both in vivo and in vitro and the most important findings about its behaviour in cancer dynamics. The Soluble E-Cadherin The E-cadherins (E-cad), or "classical" cadherins of type I, belong to the large family of cadherins, transmembrane or membrane-associated glycoproteins, mediating cell-cell adhesion and playing a pivotal role in epithelial cell behaviour and tissue morphogenesis/remodelling (reviewed in Other mechanisms potentially influencing E-cad normal functions such as its binding to other proteins include the levels of its phosphorylation together with specific proteolytic events At present, serum levels of sE-cad are known to increase in patients affected by cancer (e.g., breast, gastric, and colorectal cancers; Table 1) in respect to healthy patients, so that there is a growing interest in sE-cad as "candidate sentinel molecule" in cancer research (reviewed by Generally, since the first observations in 1990, the global decrease in E-cad in dissociating/metastasising cancer cells was accompanied by an increase in sE-cad fragments in patient sera, so that the first emerging idea was to consider the soluble sE-cad as originating from the rapid turnover of tumor cells and to relate the sE-cad concentration to the tumor size. Here, we report proteomics applied to the characterization of sE-cad amount in three solid cancers (breast, gastric, and colorectal cancers) and describe the most common techniques adopted since sE-cad discovery. Since sE-cad presence is not only limited to these three pathologies, we also briefly summarized the findings of other works in a recapitulative table Proteomics Approaches Applied to Cadherin Characterization Western Blotting (WB). In most reports, in patients, the sE-cad amount is also evaluated with WB after protein separation by one-dimensional acrylamide gel electrophoresis (1-DE), and it can be compared with the full length E-cad expression, which in turn is analysed by immunostaining in situ. WB analyses reveal the presence of multiple bands, among which are the full length E-cad at 120 kDa and the sEcad at 80 kDa. Reverse Phase Protein Array (RPPA). Another targeted approach was used by Perez-Rivas et al. Soluble E-Cadherin in Breast Cancer In BC patients, first studies started in 2005 when Hofmann and colleagues measured sE-cad levels in sera of 133 patients before and after neoadjuvant chemotherapy with an enzymebased immunoassay technique, and they positively correlated them with the pre-and posttherapeutic tumor size as well as the disease-free interval [34] evaluated by 1-DE and WB (anti-HECD-1) the release of sE-cad in the media of MCF-7/AZ BC cells grown in presence or absence of the nerve growth factor (NGF), a small secreted protein that is important for the development and survival of certain target neurons, and their results supported a relation between sE-cad levels and the BC cell acquisition of an invasive phenotype. In order to identify markers for BC patient response to surgery, the following analyses were addressed to characterize the differential serum proteomes "before versus after surgery" by RPP
