Sialic Acids Sweeten a Tumor's Life

Abstract

Over four decades ago, specific tumor characteristics were ascribed to the increased expression of sialic acid sugars on the surface of cancer cells, and this led to the definition of sialic acids as potential therapeutic targets. Recent advances in glycobiology and cancer research have defined the key processes underlying aberrant expression of sialic acids in cancer, and its consequences, more precisely. These consequences include effects on tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Collectively, these novel insights provide further rationale for the design and development of therapeutic approaches that interfere with excessively high expression of sialic acids in cancer cells. Strategies to target aberrant sialylation in cancer, however, have evolved comparatively slowly. Here, we review recent findings that emphasize the detrimental effects of hypersialylation on multiple aspects of tumor growth and behavior. We also discuss novel therapeutic strategies. Cancer Res; 74(12); 3199-204. Ó2014 AACR.

Variation in Carbohydrates between Cancer and Normal Cell Membranes Revealed by Super‐Resolution Fluorescence Imaging

“…Thus, previous studies have primarily focused on a limited type of glycosylation events that impart tumor cell properties. Some common alterations of glycosylation have shown to generally accompany with tumorigenesis and metastasis, such as, increase in branches of N‐linked oligoaccharides,7, 8 changed sialylation on certain proteins or antigens,5, 9, 10 abnormal biosynthesis of O‐linked oligosaccharides 11, 12. Owing to the complexity and variability of carbohydrate structures, the cancer‐associated carbohydrate chains have no general changed feature.…”

Precision glycocalyx editing as a strategy for cancer immunotherapy

“…The "sialome" is a central axis of immune modulation that has not yet been explored in the context of cancer therapy (15)(16)(17). When sufficiently abundant, glycans terminating in sialic acid residues create a signature of healthy self that suppresses immune activation via several pathways (18).…”

“…Up-regulation of sialosides has long been correlated with poor prognosis and decreased immunogenicity of tumors (16,18,20), but the mechanistic significance of this widespread tumor phenotype was unclear. Several recent studies implicate cancer hypersialylation as a mechanism of immune evasion mediated by Siglecs (21)(22)(23)(24)(25)(26).…”

ST6Gal-I Predicts Postoperative Clinical Outcome for Patients with Localized Clear-cell Renal Cell Carcinoma

“…The functional contribution of ST6Gal-I to a malignant phenotype has yet to be elucidated; however, escape from apoptosis, metastasis formation, and resistance to therapy may play a prominent role (Liu et al, 2011;Swindall and Bellis, 2011;Swindall et al, 2013;Bull et al, 2014). Elucidation of the exact mechanisms by which these occur has not been as straightforward.…”

“…This Golgi enzyme adds the negatively charged sugar, sialic acid, in an α2-6 linkage to the termini of N-glycans (Harduin-Lepers et al, 2001). Accumulating evidences indicate that higher intratumor expression levels of ST6Gal-I are indicator of poor prognosis in a variety of human cancers (Bull et al, 2014). Despite this well-known association with cancer aggressiveness, the potential role of ST6Gal-I in the pathogenesis and prognosis of ccRCC remains unknown.…”