O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy

Cheng, Yanru; Li, Honglun; Li, Jianlin; Li, Jisheng; Gao, Yan; Liu, Baodong

doi:10.3892/ol.2016.4647

Cited by 12 publications

(6 citation statements)

References 34 publications

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“…As O-GlcNAcylation is reversible, the inhibition of the OGA through the drug Thiamet-G, which results in elevated steady-state O-GlcNAcylation, enhanced the invasion in vitro of human thyroid anaplastic cancer 8305C cells. These results are consistent with prior studies showing that the downregulation of OGA results in the activation of Akt1 in thyroid anaplastic cells [ 86 ] and that O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy [ 87 ]. Thus, phosphorylation and O-GlcNAcylation together may regulate PI3K/Akt signaling, and drugs targeted to affect this pathway may be useful for the treatment of thyroid anaplastic cancer.…”

Section: Phosphorylationsupporting

confidence: 93%

Posttranslational Modifications in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, Classification, and Treatment

Broekhuis

James

Cummings

et al. 2022

Cancers

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There is evidence that posttranslational modifications, including phosphorylation, acetylation, methylation, ubiquitination, sumoylation, glycosylation, and succinylation, may be involved in thyroid cancer. We review recent reports supporting a role of posttranslational modifications in the tumorigenesis of thyroid cancer, sensitivity to radioiodine and other types of treatment, the identification of molecular treatment targets, and the development of molecular markers that may become useful as diagnostic tools. An increased understanding of posttranslational modifications may be an important supplement to the determination of alterations in gene expression that has gained increasing prominence in recent years.

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Section: Phosphorylationsupporting

confidence: 93%

Posttranslational Modifications in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, Classification, and Treatment

Broekhuis

James

Cummings

et al. 2022

Cancers

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“…OGT overexpression (OE) is advantageous to cancer cells. In particular, OGT OE promotes proliferation of colon (73), gastric (74,75), thyroid (76), breast (77) and liver cancer cells (78). In addition, OGT OE has been shown to enhance invasion / motility of cancer cells of breast (79,80), cervix (81) and thyroid (82).…”

Section: Overexpression Of Ogt Promotes Malignant Phenotype Of Cancer Cellsmentioning

confidence: 99%

O-GlcNAc Transferase – An Auxiliary Factor or a Full-blown Oncogene?

Itkonen

Loda

Mills

2021

Molecular Cancer Research

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The β-linked N-acetyl-D-glucosamine (GlcNAc) is a post-translational modification of serine and threonine residues catalyzed by the enzyme O-GlcNAc transferase (OGT). Increased OGT expression is a feature of most human cancers and inhibition of OGT decreases cancer cell proliferation. Anti-proliferative effects are attributed to post-translational modifications of known regulators of cancer cell proliferation, such as MYC, FOXM1 and EZH2. In general, OGT amplifies cell-specific phenotype, for example, OGT overexpression enhances reprogramming efficiency of mouse embryonic fibroblasts into stem cells. Genomewide screens suggest that certain cancers are particularly dependent on OGT, and understanding these addictions is important when considering OGT as a target for cancer therapy. The O-GlcNAc modification is involved in most cellular processes, which raises concerns of on-target undesirable effects of OGT targeting therapy. Yet, emerging evidence suggest that, much like proteasome inhibitors, specific compounds targeting OGT elicit selective anti-proliferative effects in cancer cells, and can prime malignant cells to other treatments. It is therefore essential to gain mechanistic insights on substrate specificity for OGT, develop reagents to more specifically enrich for O-GlcNAc modified proteins, identify O-GlcNAc 'readers' and develop OGT small molecule inhibitors. Here, we review the relevance of OGT in cancer progression and the potential targeting of this metabolic enzyme as a putative oncogene. Contrasting the functions of any candidate oncogene between normal and cancer cells is rarely done, but only by understanding the normal functions of a given factor, it is possible to understand these functions gone awry. Here we review oncogenic functions of OGT.

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“…Both OGT overexpression and OGA inhibition increased thyroid cell proliferation, while the opposite effect, attenuated cell proliferation, was observed in OGT-silenced cells. Higher O -GlcNAc level was associated with more intensive colony formation and thyroid cell mobility [ 114 ].…”

Section: Glycosylation In Thyroid Pathologymentioning

confidence: 99%

Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders

Ząbczyńska

Kozłowska

Pocheć

2018

IJMS

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The key proteins responsible for hormone synthesis in the thyroid are glycosylated. Oligosaccharides strongly affect the function of glycosylated proteins. Both thyroid-stimulating hormone (TSH) secreted by the pituitary gland and TSH receptors on the surface of thyrocytes contain N-glycans, which are crucial to their proper activity. Thyroglobulin (Tg), the protein backbone for synthesis of thyroid hormones, is a heavily N-glycosylated protein, containing 20 putative N-glycosylated sites. N-oligosaccharides play a role in Tg transport into the follicular lumen, where thyroid hormones are produced, and into thyrocytes, where hyposialylated Tg is degraded. N-glycans of the cell membrane transporters sodium/iodide symporter and pendrin are necessary for iodide transport. Some changes in glycosylation result in abnormal activity of the thyroid and alteration of the metabolic clearance rate of hormones. Alteration of glycan structures is a pathological process related to the progression of chronic diseases such as thyroid cancers and autoimmunity. Thyroid carcinogenesis is accompanied by changes in sialylation and fucosylation, β1,6-branching of glycans, the content and structure of poly-LacNAc chains, as well as O-GlcNAcylation, while in thyroid autoimmunity the main processes affected are sialylation and fucosylation. The glycobiology of the thyroid gland is an intensively studied field of research, providing new data helpful in understanding the role of the sugar component in thyroid protein biology and disorders.

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O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy

Abstract: Abstract. O-linked N-acetylglucosamine (O-GlcNAc

Cited by 12 publications

References 34 publications

Posttranslational Modifications in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, Classification, and Treatment

Posttranslational Modifications in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, Classification, and Treatment

O-GlcNAc Transferase – An Auxiliary Factor or a Full-blown Oncogene?

Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders

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