Targeting Phosphorylation and Glycosylation of Membrane-Bound Oncogenic Drivers, Receptors and Adhesion Molecules to Control Constitutive Proliferation of Human Carcinoma Cells

With the advent of next generation technologies, genome-wide association studies (GWAS) have provided abundant clues regarding under- or over-expressed glycosyltransferase genes and their encoded products in O-glycosylation of key cell-surface receptors with oncogenic capacities such as the epidermal growth factor receptors (EGFRs). The O-glycosylation and N-glycosylation on the extracellular domain of EGFRs may regulate the phosphorylation of their tyrosine kinase domain in a constitutive manner, and impact the multimerization and clustering of EGFR in pathologic phenotypes of breast, cervical and endometrial cancers. As such, both O-glycosylation and N-glycosylation processes are equally important in shaping the conformation and underlying activation status of EGFR-family and other cell surface glycoprotein members.

The relationship between glycosylation and phosphorylation of oncogenic membrane (and surface proteins) will therefore be the main focus of this Research Topic. In addition, the Topic will examine the combined therapeutic evaluation of glycosylation inhibitors targeting O- and/or N-glycosylation, and tyrosine kinase inhibitors and their cumulative impact in adjuvant and neoadjuvant, curative/salvage (main chemotherapy) to down-regulate constitutive activation of EGFRs’ tyrosine kinase activity. Other surface glycoproteins of neoplastic cells that govern cell-cell interactions, in particular mucins and cell-adhesion proteins (for instance cadherins and integrins) in ductal breast cancer, are expected to express glycoprotein alterations that accompany the epithelial-mesenchymal transition (EMT) occurring during metastasis. Studies on death-receptors of the tumor-necrosis factor (TNF) family and their occurrence as abnormally glycosylated cell-surface proteins will also be welcome in the Topic. We also wish to include clinical studies to bridge the gap between molecular studies on cell lines and clinical research.

To cover the widest range of approaches in women’s cancer glycobiology and identify potential neoadjuvant, curative and adjuvant compounds and molecules, we intend to solicit, in addition to regular research papers, novel methods, short communications, clinical cases, experimental models, opinions and reviews.