The Role of Sialyl-Tn in Cancer

Munkley, Jennifer

doi:10.3390/ijms17030275

Cited by 173 publications

(157 citation statements)

References 83 publications

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“…Increased sialylation can increase local negative charges to physically disrupt cell-cell adhesion, and promote detachment from the tumour mass through electrostatic repulsion [87]. Consistent with this, expression of the cancer-associated sTn-antigen reduces cell adhesion in prostate cancer and increases migration and invasion in breast and gastric carcinoma [88–93]. Similarly, ectopic expression of the sialytransferase ST6GAL1 in breast cancer cells has been shown to reduce cell adhesion [94].…”

Section: Activating Invasion and Metastasismentioning

confidence: 95%

Hallmarks of glycosylation in cancer

2016

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Aberrant glycosylation plays a fundamental role in key pathological steps of tumour development and progression. Glycans have roles in cancer cell signalling, tumour cell dissociation and invasion, cell-matrix interactions, angiogenesis, metastasis and immune modulation. Aberrant glycosylation is often cited as a ‘hallmark of cancer’ but is notably absent from both the original hallmarks of cancer and from the next generation of emerging hallmarks. This review discusses how glycosylation is clearly an enabling characteristic that is causally associated with the acquisition of all the hallmark capabilities. Rather than aberrant glycosylation being itself a hallmark of cancer, another perspective is that glycans play a role in every recognised cancer hallmark.

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Section: Activating Invasion and Metastasismentioning

confidence: 95%

Hallmarks of glycosylation in cancer

2016

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“…Non-mucin O-glycans include α-attached via O-mannose, α-linked O-fucose, and the β-linked N-acetylglucosamine (O-GlcNAc) [112]. Small or truncated O-glycans are increased in different types of tumors, including gastric, colon, breast, and pancreatic cancer [113, 114], and their production is associated with a poor prognosis and metastasis [115]. …”

Section: Hypoxia Changes Membrane Glycoconjugates In Tumor Cellsmentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

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“…This can be further modified by the addition of terminal Gal (galactose), GlcNAc and sialic acid moieties. O-glycan biosynthesis ST6GALNAC1 Sialylation of O-glycans to produce the cancer-associated sTn antigen (Munkley 2016) Associated with poor prognosis in numerous cancer types (Munkley 2016). Promotes tumourigenicity and metastasis in breast and gastric cancer cells (Julien et al 2006, Ozaki et al 2012 ST6GALNAC1 shown to synthesise sTn and reduce cell adhesion in prostate cancer cells (Munkley et al 2015c, Munkley & Elliott 2016b.…”

Section: Figurementioning

confidence: 99%

“…We also identified the sialyltransferase ST6GalNAc1 as being directly regulated by androgens in prostate cancer cells (Munkley et al 2015c. ST6GalNAc1 adds sialic acid to the Tn antigen to produce the cancer-associated onco-foetal sialyl-Tn (sTn) antigen, which is linked to poor prognosis in numerous cancer types (Munkley 2016). STn is a truncated O-glycan containing a sialic acid α-2,6 linked to GalNAc α-O-Ser/Thr and has been shown to promote tumour growth and metastasis in mouse models (Julien et al 2006, Ozaki et al 2012.…”

Section: :3mentioning

confidence: 99%

“…Expression of ST6GAL1 is linked to EMT and 24:3 malignancy, but the mechanisms driving this transition remain to be explored (Lu et al 2014). Increased sialylation can influence cancer cell metastasis, invasion and survival (Munkley 2016). In prostate cancer cells, increased sialylation of PSA is linked to more aggressive disease (Llop et al 2016, Munkley et al 2016a).…”

Section: N-glycan Biosynthesis (Ost Complex N-glycan Processing)mentioning

confidence: 99%

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Glycosylation is a global target for androgen control in prostate cancer cells

Munkley¹

2017

Endocrine-Related Cancer

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Changes in glycan composition are common in cancer and can play important roles in all of the recognised hallmarks of cancer. We recently identified glycosylation as a global target for androgen control in prostate cancer cells and further defined a set of 8 glycosylation enzymes (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3), which are also significantly upregulated in prostate cancer tissue. These 8 enzymes are under direct control of the androgen receptor (AR) and are linked to the synthesis of important cancer-associated glycans such as sialyl-Tn (sTn), sialyl LewisX (SLeX), O-GlcNAc and chondroitin sulfate. Glycosylation has a key role in many important biological processes in cancer including cell adhesion, migration, interactions with the cell matrix, immune surveillance, cell signalling and cellular metabolism. Our results suggest that alterations in patterns of glycosylation via androgen control might modify some or all of these processes in prostate cancer. The prostate is an abundant secretor of glycoproteins of all types, and alterations in glycans are, therefore, attractive as potential biomarkers and therapeutic targets. Emerging data on these often overlooked glycan modifications have the potential to improve risk stratification and therapeutic strategies in patients with prostate cancer.

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The Role of Sialyl-Tn in Cancer

Cited by 173 publications

References 83 publications

Hallmarks of glycosylation in cancer

Hallmarks of glycosylation in cancer

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Glycosylation is a global target for androgen control in prostate cancer cells

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