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Review
. 2022 Aug 29:9:962908.
doi: 10.3389/fmolb.2022.962908. eCollection 2022.

ST6Gal1: Oncogenic signaling pathways and targets

Sajina Gc  1 , Susan L Bellis  1 , Anita B Hjelmeland  1
Affiliations
Review

ST6Gal1: Oncogenic signaling pathways and targets

Sajina Gc et al. Front Mol Biosci. .

Abstract

The Golgi-sialyltransferase ST6Gal1 (βgalactosidase α2,6 sialyltransferase 1), adds the negatively charged sugar, sialic acid, to the terminal galactose of N-glycosylated proteins. Upregulation of ST6Gal1 is observed in many malignancies, and a large body of research has determined that ST6Gal1-mediated α2,6 sialylation impacts cancer hallmarks. ST6Gal1 affects oncogenic behaviors including sustained proliferation, enhanced self-renewal, epithelial-to-mesenchymal transition, invasion, and chemoresistance. However, there are relatively few ST6GaL1 related signaling pathways that are well-established to mediate these biologies: greater delineation of specific targets and signaling mechanisms that are orchestrated by ST6Gal1 is needed. The aim of this review is to provide a summary of our current understanding of select oncogenic signaling pathways and targets affected by ST6Gal1.

Keywords: ST6GAL1; cancer; pathways affecting cancer; sialylation; sialyltransferase; targets.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Posttranslational Modification of N-Glycoproteins in Golgi. (A) Mature glycan linked to dolichol phosphate is added to the protein synthesized in rough endoplasmic reticulum (i). The glycoproteins are modified via trimming in cis-Golgi (ii), extension in median Golgi (iii) and terminal sialylation by ST6Gal1 among other sialyltransferases in trans-Golgi (iv). The mature proteins are transported in vesicles (v) to the membrane (vi). (B) ST6Gal1 adds α2,6 linked terminal sialic acid to the N-linked glycoproteins using CMP-Sialic acid as a donor. The schematic diagram was created using Biorender (https://biorender.com).
FIGURE 2
FIGURE 2
ST6Gal1-mediated Signaling Cascades in Cancer. The membrane bound N-glycoproteins synthesized and processed in secretory pathways (including Fas, TNFR1, β1-integrin, PECAM, VEGFR2 and EGFR among others) are α2,6 sialylated by ST6Gal1. This can affect protein cell surface retention, stability, clustering and/or activation. Through direct and indirect signaling pathways, ST6Gal1 promotes oncogenic characteristics in many cancers. The pink diamond represents α2,6 linked sialic acid, although the full glycan structure is not shown for simplification. The figure was created using Biorender (https://biorender.com).
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