Insights into the role of sialylation in cancer progression and metastasis

Abstract

Upregulation of sialyltransferases—the enzymes responsible for the addition of sialic acid to growing glycoconjugate chains—and the resultant hypersialylation of up to 40–60% of tumour cell surfaces are established hallmarks of several cancers, including lung, breast, ovarian, pancreatic and prostate cancer. Hypersialylation promotes tumour metastasis by several routes, including enhancing immune evasion and tumour cell survival, and stimulating tumour invasion and migration. The critical role of enzymes that regulate sialic acid in tumour cell growth and metastasis points towards targeting sialylation as a potential new anti-metastatic cancer treatment strategy. Herein, we explore insights into the mechanisms by which hypersialylation plays a role in promoting metastasis, and explore the current state of sialyltransferase inhibitor development.

Rola glikanów w rozwoju i progresji nowotworu. Zastosowania kliniczne

“…Uważa się, że oporność na chemioterapię może być wynikiem hipersjalilacji komórek nowotworowych. Silnie podwyższona ekspresja kwasów sjalowych na powierzchni komórek nowotworowych może stanowić fizyczną barierę, blokując dyfuzję leku do wnętrza komórki [73]. Wykazano, że nadekspresja ST6Gal-I osłabia apoptozę komórek raka jajnika indukowaną paklitakselem oraz adriamycyną [74].…”

Aberrant Sialylation in Cancer: Biomarker and Potential Target for Therapeutic Intervention?

“…Several key reviews have thoroughly described the role of aberrant glycosylation and sialylation in cancer [ 5 , 6 , 7 ]. In this review, we summarize recent advances on the regulation of ST expression in cancer and explore the mechanisms by which STs promote cancer progression through activation of invasion and metastasis, stimulation of angiogenesis, drug resistance, immune evasion and tumor cell survival.…”

Abnormal Glycosylation of Cancer Stem Cells and Targeting Strategies

“…The glycan chains on cancer cells regulate a range of pathological processes, including cell-cell interaction, cell adhesion, receptor activation and signal transduction (14). The main terminal sugar of the cell surface glycan chain is neuraminic acid (sialic acid; SA), which is being studied extensively in tumor biology (16). The overexpression of terminal glycan SA has also been linked to cancer malignancy and metastasis (16,17).…”

“…The main terminal sugar of the cell surface glycan chain is neuraminic acid (sialic acid; SA), which is being studied extensively in tumor biology (16). The overexpression of terminal glycan SA has also been linked to cancer malignancy and metastasis (16,17). Moreover, hypersialylation in cancer cells promotes cell migration (18) and apoptosis resistance (19), which lead to tumor growth and poor prognosis (16).…”

“…The overexpression of terminal glycan SA has also been linked to cancer malignancy and metastasis (16,17). Moreover, hypersialylation in cancer cells promotes cell migration (18) and apoptosis resistance (19), which lead to tumor growth and poor prognosis (16). CSCs may be further distinguished from differentiated cancer cells by the expression of carbohydrate antigens (20,21), and the Nglycosylation of glycoproteins of CSCs has been related to drug resistance mechanisms (22).…”