Regulation of ST6GAL1 sialyltransferase expression in cancer cells.

The ST6GAL1 sialyltransferase, which adds α2-6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics.

Sox2 promotes expression of the ST6Gal-I glycosyltransferase in ovarian cancer cells.

Background: The ST6Gal-I glycosyltransferase, which adds α2-6-linked sialic acids to N-glycosylated proteins is upregulated in a wide range of malignancies including ovarian cancer. Prior studies have shown that ST6Gal-I-mediated sialylation of select surface receptors remodels intracellular signaling to impart cancer stem cell (CSC) characteristics. However, the mechanisms that contribute to ST6Gal-I expression in stem-like cancer cells are poorly understood.

Transfer of Functional Cargo in Exomeres.

Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function. Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes. Exomeres are enriched in Argonaute 1-3 and amyloid precursor protein.

The ST6Gal-I sialyltransferase protects tumor cells against hypoxia by enhancing HIF-1α signaling.

Aberrant cell surface glycosylation is prevalent in tumor cells, and there is ample evidence that glycans have functional roles in carcinogenesis. Nonetheless, many molecular details remain unclear. Tumor cells frequently exhibit increased α2-6 sialylation on -glycans, a modification that is added by the ST6Gal-I sialyltransferase, and emerging evidence suggests that ST6Gal-I-mediated sialylation promotes the survival of tumor cells exposed to various cell stressors.

ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Gemcitabine, as a single agent or in combination therapy, remains the frontline chemotherapy despite its limited efficacy due to or acquired chemoresistance. There is an acute need to decipher mechanisms underlying chemoresistance and identify new targets to improve patient outcomes.

and regulate vacuolar size and function in .

The yeast vacuole plays key roles in cellular stress responses. Here, we show that deletion of , the fission yeast homolog of the Chediak-Higashi Syndrome / gene, increases vacuolar size, similar to deletion of the Rab4 homolog . Overexpression of lvs1-YFP rescued vacuolar size in cells, but ypt4-YFP did not rescue , suggesting that may act downstream of .

The Glycosyltransferase ST6Gal-I Protects Tumor Cells against Serum Growth Factor Withdrawal by Enhancing Survival Signaling and Proliferative Potential.

A hallmark of cancer cells is the ability to survive and proliferate when challenged with stressors such as growth factor insufficiency. In this study, we report a novel glycosylation-dependent mechanism that protects tumor cells from serum growth factor withdrawal. Our results suggest that the β-galactoside α-2,6-sialyltransferase 1 (ST6Gal-I) sialyltransferase, which is up-regulated in numerous cancers, promotes the survival of serum-starved cells.