Dataset Information

Galectin-7 in Epithelial Homeostasis and Carcinomas.

ABSTRACT: Galectins are small unglycosylated soluble lectins distributed both inside and outside the cells. They share a conserved domain for the recognition of carbohydrates (CRD). Although galectins have a common affinity for ?-galatosides, they exhibit different binding preferences for complex glycans. First described twenty years ago, galectin-7 is a prototypic galectin, with a single CRD, able to form divalent homodimers. This lectin, which is mainly expressed in stratified epithelia, has been described in epithelial tissues as being involved in apoptotic responses, in proliferation and differentiation but also in cell adhesion and migration. Most members of the galectins family have been associated with cancer biology. One of the main functions of galectins in cancer is their immunomodulating potential and anti-angiogenic activity. Indeed, galectin-1 and -3, are already targeted in clinical trials. Another relevant function of galectins in tumour progression is their ability to regulate cell migration and cell adhesion. Among these galectins, galectin-7 is abnormally expressed in various cancers, most prominently in carcinomas, and is involved in cancer progression and metastasis but its precise functions in tumour biology remain poorly understood. In this issue, we will focus on the physiological functions of galectin-7 in epithelia and present the alterations of galectin-7 expression in carcinomas with the aim to describe its possible functions in tumour progression.

SUBMITTER: Advedissian T

PROVIDER: S-EPMC5751359 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Galectin-7 in Epithelial Homeostasis and Carcinomas.

Advedissian Tamara T Deshayes Frédérique F Viguier Mireille M

International journal of molecular sciences 20171219 12

Galectins are small unglycosylated soluble lectins distributed both inside and outside the cells. They share a conserved domain for the recognition of carbohydrates (CRD). Although galectins have a common affinity for β-galatosides, they exhibit different binding preferences for complex glycans. First described twenty years ago, galectin-7 is a prototypic galectin, with a single CRD, able to form divalent homodimers. This lectin, which is mainly expressed in stratified epithelia, has been descri ...[more]

PMID: 29257082

Similar Datasets

Project description:The significance of the phenotypic plasticity afforded by epithelial-mesenchymal transition (EMT) for cancer progression and drug resistance remains to be fully elucidated in the clinic. We evaluated epithelial-mesenchymal phenotypic characteristics across a range of tumor histologies using a validated, high-resolution digital microscopic immunofluorescence assay (IFA) that incorporates β-catenin detection and cellular morphology to delineate carcinoma cells from stromal fibroblasts and that quantitates the individual and colocalized expression of the epithelial marker E-cadherin (E) and the mesenchymal marker vimentin (V) at subcellular resolution ("EMT-IFA"). We report the discovery of β-catenin+ cancer cells that coexpress E-cadherin and vimentin in core-needle biopsies from patients with various advanced metastatic carcinomas, wherein these cells are transitioning between strongly epithelial and strongly mesenchymal-like phenotypes. Treatment of carcinoma models with anticancer drugs that differ in their mechanism of action (the tyrosine kinase inhibitor pazopanib in MKN45 gastric carcinoma xenografts and the combination of tubulin-targeting agent paclitaxel with the BCR-ABL inhibitor nilotinib in MDA-MB-468 breast cancer xenografts) caused changes in the tumor epithelial-mesenchymal character. Moreover, the appearance of partial EMT or mesenchymal-like carcinoma cells in MDA-MB-468 tumors treated with the paclitaxel-nilotinib combination resulted in upregulation of cancer stem cell (CSC) markers and susceptibility to FAK inhibitor. A metastatic prostate cancer patient treated with the PARP inhibitor talazoparib exhibited similar CSC marker upregulation. Therefore, the phenotypic plasticity conferred on carcinoma cells by EMT allows for rapid adaptation to cytotoxic or molecularly targeted therapy and could create a form of acquired drug resistance that is transient in nature. SIGNIFICANCE: Despite the role of EMT in metastasis and drug resistance, no standardized assessment of EMT phenotypic heterogeneity in human carcinomas exists; the EMT-IFA allows for clinical monitoring of tumor adaptation to therapy.

Project description:Identification of interactors is a major goal in cell biology. Not only protein-protein but also protein-carbohydrate interactions are of high relevance for signal transduction in biological systems. Here, we aim to identify novel interacting binding partners for the ?-galactoside-binding proteins galectin-1 (Gal-1) and galectin-3 (Gal-3) relevant in the context of the eye disease proliferative vitreoretinopathy (PVR). PVR is one of the most common failures after retinal detachment surgeries and is characterized by the migration, adhesion, and epithelial-to-mesenchymal transition of retinal pigment epithelial cells (RPE) and the subsequent formation of sub- and epiretinal fibrocellular membranes. Gal-1 and Gal-3 bind in a dose- and carbohydrate-dependent manner to mesenchymal RPE cells and inhibit cellular processes like attachment and spreading. Yet knowledge about glycan-dependent interactors of Gal-1 and Gal-3 on RPE cells is very limited, although this is a prerequisite for unraveling the influence of galectins on distinct cellular processes in RPE cells. We identify here 131 Gal-3 and 15 Gal-1 interactors by galectin pulldown experiments combined with quantitative proteomics. They mainly play a role in multiple binding processes and are mostly membrane proteins. We focused on two novel identified interactors of Gal-1 and Gal-3 in the context of PVR: the low-density lipoprotein receptor LRP1 and the platelet-derived growth factor receptor ? PDGFRB. Addition of exogenous Gal-1 and Gal-3 induced cross-linking with LRP1/PDGFRB and integrin-?1 (ITGB1) on the cell surface of human RPE cells and induced ERK/MAPK and Akt signaling. Treatment with kifunensine, an inhibitor of complex-type N-glycosylation, weakened the binding of Gal-1 and Gal-3 to these interactors and prevented lattice formation. In conclusion, the identified specific glycoprotein ligands shed light into the highly specific binding of galectins to dedifferentiated RPE cells and the resulting prevention of PVR-associated cellular events.

Project description:IntroductionIntegrating additional factors into the International Federation of Gynecology and Obstetrics (FIGO) staging system is needed for accurate patient classification and survival prediction. In this study, we tested machine learning as a novel tool for incorporating additional prognostic parameters into the conventional FIGO staging system for stratifying patients with epithelial ovarian carcinomas and evaluating their survival.Material and methodsCancer-specific survival data for epithelial ovarian carcinomas were extracted from the Surveillance, Epidemiology, and End Results (SEER) program. Two datasets were constructed based upon the year of diagnosis. Dataset 1 (39 514 cases) was limited to primary tumor (T), regional lymph nodes (N) and distant metastasis (M). Dataset 2 (25 291 cases) included additional parameters of age at diagnosis (A) and histologic type and grade (H). The Ensemble Algorithm for Clustering Cancer Data (EACCD) was applied to generate prognostic groups with depiction in dendrograms. C-indices provided dendrogram cutoffs and comparisons of prediction accuracy.ResultsDataset 1 was stratified into nine epithelial ovarian carcinoma prognostic groups, contrasting with 10 groups from FIGO methodology. The EACCD grouping had a slightly higher accuracy in survival prediction than FIGO staging (C-index = 0.7391 vs 0.7371, increase in C-index = 0.0020, 95% confidence interval [CI] 0.0012-0.0027, p = 1.8 × 10-7 ). Nevertheless, there remained a strong inter-system association between EACCD and FIGO (rank correlation = 0.9480, p = 6.1 × 10-15 ). Analysis of Dataset 2 demonstrated that A and H could be smoothly integrated with the T, N and M criteria. Survival data were stratified into nine prognostic groups with an even higher prediction accuracy (C-index = 0.7605) than when using only T, N and M.ConclusionsEACCD was successfully applied to integrate A and H with T, N and M for stratification and survival prediction of epithelial ovarian carcinoma patients. Additional factors could be advantageously incorporated to test the prognostic impact of emerging diagnostic or therapeutic advances.

Dataset Information

Galectin-7 in Epithelial Homeostasis and Carcinomas.

Publications

Galectin-7 in Epithelial Homeostasis and Carcinomas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets