C1GALT1 predicts poor prognosis and is a potential therapeutic target in head and neck cancer

Lin, Mei-Chun; Chien, P.-H.; Wu, Hsin‐Yi; Chen, Syue-Ting; Juan, Hsueh‐Fen; Lou, Pei‐Jen; Huang, Min-Chuan

doi:10.1038/s41388-018-0375-0

Cited by 44 publications

(69 citation statements)

References 39 publications

(42 reference statements)

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“…Lin et al investigated the role of C1GALT1 in head and neck squamous carcinoma (HNSCC). C1GALT1 was found to be an independent attributor for poor OAS of HNSCC patients [54]. C1GALT1 affected cell viability, proliferation, invasion, tumor growth, and lung metastasis in HNSCC cells.…”

Section: Core-1 Synthase Behaves Differently In Different Cancersmentioning

confidence: 87%

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Gupta

Leon

Rauth

et al. 2020

Cells

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Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is directed by different glycosyltransferases, depending on the cell in which it is expressed. These small carbohydrate molecules consist of multiple glycan families that facilitate cell–cell interactions, protein interactions, and downstream signaling. An alteration of several types of O-glycan core structures have been implicated in multiple cancers, largely due to differential glycosyltransferase expression or activity. Consequently, aberrant O-linked glycosylation has been extensively demonstrated to affect biological function and protein integrity that directly result in cancer growth and progression of several diseases. Herein, we provide a comprehensive review of several initiating enzymes involved in the synthesis of O-linked glycosylation that significantly contribute to a number of different cancers.

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Section: Core-1 Synthase Behaves Differently In Different Cancersmentioning

confidence: 87%

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Gupta

Leon

Rauth

et al. 2020

Cells

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“…Moreover, in some models the mere abrogation of T-synthase/COSMC is sufficient to induce oncogenic features and to augment tumorigenesis of otherwise healthy cells (12,52). In contrast, enhanced T antigen expression also correlates to bad prognosis and oncogenesis in, for instance, breast (31,53,54) and head and neck cancer (55). Strikingly, although Du et al observed reduced breast cancer growth upon COSMC disruption, they also noticed an inhibition of the MAPK pathway similar to our findings (31) (Supplementary Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Tn Antigen Expression Contributes to an Immune Suppressive Microenvironment and Drives Tumor Growth in Colorectal Cancer

et al. 2020

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Expression of the tumor-associated glycan Tn antigen (αGalNAc-Ser/Thr) has been correlated to poor prognosis and metastasis in multiple cancer types. However, the exact mechanisms exerted by Tn antigen to support tumor growth are still lacking. One emerging hallmark of cancer is evasion of immune destruction. Although tumor cells often exploit the glycosylation machinery to interact with the immune system, the contribution of Tn antigen to an immunosuppressive tumor microenvironment has scarcely been studied. Here, we explored how Tn antigen influences the tumor immune cell composition in a colorectal cancer (CRC) mouse model. CRISPR/Cas9-mediated knock out of the C1galt1c1 gene resulted in elevated Tn antigen levels on the cell surface of the CRC cell line MC38 (MC38-Tn high). RNA sequencing and subsequent GO term enrichment analysis of our Tn high glycovariant not only revealed differences in MAPK signaling and cell migration, but also in antigen processing and presentation as well as in cytotoxic T cell responses. Indeed, MC38-Tn high tumors displayed increased tumor growth in vivo, which was correlated with an altered tumor immune cell infiltration, characterized by reduced levels of cytotoxic CD8 + T cells and enhanced accumulation of myeloid-derived suppressor cells. Interestingly, no systemic differences in T cell subsets were observed. Together, our data demonstrate for the first time that Tn antigen expression in the CRC tumor microenvironment affects the tumor-associated immune cell repertoire.

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“…41 Conversely, several recent studies unexpectedly found that loss of T-synthase, but not Cosmc, resulted in Tn antigen expression and subsequently delayed tumor development including breast, head and neck, and hepatocellular carcinoma. [21][22][23] It appears that aberrant O-glycosylation may exert opposite effects in different types of cancers, which requires more investigations.…”

Section: Discussionmentioning

confidence: 99%

“…The prevailing studies supported a tumorpromoting role for aberrant O-glycosylation in a broad range of human cancers, including pancreatic, colorectal, and gastric cancer, [17][18][19][20] whereas several recent reports indicated rather an opposite effect of aberrant O-glycosylation, which was shown to delay tumor development in breast, liver, and head and neck cancers. [21][22][23] Overall, there is much to be learned about the impact of aberrant O-glycosylation on breast cancer development.…”

Section: Introductionmentioning

confidence: 99%

<p>Cosmc Disruption-Mediated Aberrant O-glycosylation Suppresses Breast Cancer Cell Growth via Impairment of CD44</p>

Du¹,

Jia²,

Dong³

et al. 2020

CMAR

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Background: Breast cancer remains the most lethal malignancy in women worldwide. Aberrant O-glycosylation is closely related to many human diseases, including breast carcinoma; however, its precise role in cancer development is insufficiently understood. Cosmc is an endoplasmic reticulum-localized chaperone that regulates the O-glycosylation of proteins. Cosmc dysfunction results in inactive T-synthase and expression of truncated O-glycans such as Tn antigen. Here we investigated the impact of Cosmc disruption-mediated aberrant O-glycosylation on breast cancer cell development through in vitro and in vivo experiments. Materials and Methods: We deleted the Cosmc gene in two breast cancer cell lines (MCF7, T47D) using the CRISPR/Cas-9 system and then measured the expression levels of Tn antigen. The proliferation of Tn-positive cells was examined by RTCA, colony formation and in vivo experiments. The effects of Cosmc deficiency on glycoprotein CD44 and MAPK pathway were also determined. Results: Both in vitro and in vivo studies showed that Cosmc deficiency markedly suppressed breast cancer cell growth compared with the corresponding controls. Mechanistically, Cosmc disruption impaired the protein expression of CD44 and the associated MAPK signaling pathway; the latter plays a crucial role in cell proliferation. Reconstitution of CD44 substantially reversed the observed alterations, confirming that CD44 requires normal O-glycosylation for its proper expression and activation of the related signaling pathway. Conclusion: This study showed that Cosmc deficiency-mediated aberrant O-glycosylation suppressed breast cancer cell growth, which was likely mediated by the impairment of CD44 expression.

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C1GALT1 predicts poor prognosis and is a potential therapeutic target in head and neck cancer

Cited by 44 publications

References 39 publications

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

Tn Antigen Expression Contributes to an Immune Suppressive Microenvironment and Drives Tumor Growth in Colorectal Cancer

<p>Cosmc Disruption-Mediated Aberrant O-glycosylation Suppresses Breast Cancer Cell Growth via Impairment of CD44</p>

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