&lt;p&gt;Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens&lt;/p&gt;

Xu, Feng; Wang, Dong; Cui, Jianxiu; Li, Jie; Jiang, Hongchuan

doi:10.2147/cmar.s214553

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…Some experts believe that the inactivation or lack of Cosmc makes O-linked glycoproteins carry this truncated sTn glycans (24). As our recent study showed, Cosmc promoter hypermethylation could decrease the levels of Cosmc and increase Tn and sTn antigens expression in BC cells (21). Few studies have evaluated the role of sTn in the prognosis of patients with BC (25).…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, all sections were visualized with a DAB kit, and the nucleus was counterstained with hematoxylin. For positive controls, samples of Cosmc-KO MCF-7 BC cells (21) and human placenta were used for sTn and PD-L1 staining, respectively. We prepared negative controls by using PBS as a substitute for the primary antibody.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

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Mucin-type sialyl-Tn antigen is associated with PD-L1 expression and predicts poor clinical prognosis in breast cancer

Xu¹,

Zhao²,

Li³

et al. 2021

Gland Surg

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Background: A recent study showed that mucin-type sialylated O-linked glycans could induce the increased expression of PD-L1 via binding to Siglec receptors. However, the relationship between the expression of the mucin-type sialyl-Tn antigen (sTn) and PD-L1 remains unclear in breast cancer (BC).Therefore, we investigate the clinicopathological and prognostic effects of sTn expression and its relationship with PD-L1 expression in BC tissues. Methods: We retrospectively analyzed the clinical data of 380 invasive BC patients between January 2011 and January 2014. The last follow-up time was January 31, 2019 with a median follow-up of 62 months. The expression of the sTn antigen and PD-L1 in 380 tumor specimens was assessed by immunohistochemistry. Correlations between sTn/PD-L1 expression and clinicopathological features and prognoses were analyzed. Results: In BC tissues, the positive expression rate of PD-L1 (20.5%) was much lower than that of sTn (41.8%). Pearson's contingency analysis showed that sTn and PD-L1 expression in tumor tissues demonstrated a high correlation (P<0.001). High sTn expression was associated with negative ER expression (P<0.001), positive HER-2 status (P<0.001), advanced tumor stage (P<0.001), high density of CD8+ tumorinfiltrating lymphocytes (TILs) (P=0.028), and positive lymph node metastasis (P=0.002). Moreover, patients with concomitant high expression of both markers had the highest risk of relapse (P<0.001) and mortality (P<0.001). The multivariate Cox regression model revealed that positive sTn expression (HRos: 1.941,

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Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Mucin-type sialyl-Tn antigen is associated with PD-L1 expression and predicts poor clinical prognosis in breast cancer

Xu¹,

Zhao²,

Li³

et al. 2021

Gland Surg

Self Cite

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“…It was shown that hypermethylation leads to decreased expression of a chaperone that folds enzymes involved in O-glycan elongation. The absence of these elongation enzymes results in increased Tn antigen expression in cancers, which were shown to directly induce oncogenic features including cell growth and invasion [93,94]. It was also shown that activation of the oncogene Src leads to increased retrograde trafficking from Golgi to ER of GALNTs, which results in increased O-glycosylation of proteins in the ER and increased surface levels of Tn antigen [95].…”

Section: Golgi Processingmentioning

confidence: 99%

Golgi Apparatus Regulates Plasma Membrane Composition and Function

Agliarulo

Parashuraman

2022

Cells

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Golgi apparatus is the central component of the mammalian secretory pathway and it regulates the biosynthesis of the plasma membrane through three distinct but interacting processes: (a) processing of protein and lipid cargoes; (b) creation of a sharp transition in membrane lipid composition by non-vesicular transport of lipids; and (c) vesicular sorting of proteins and lipids at the trans-Golgi network to target them to appropriate compartments. We discuss the molecules involved in these processes and their importance in physiology and development. We also discuss how mutations in these molecules affect plasma membrane composition and signaling leading to genetic diseases and cancer.

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“…As these decay proteins lack the intracellular death domain that is required by downstream apoptosis signaling, the death signaling was not able to pass on, hence cell death was prevented [ 87 ]. In breast cancer MDA-MB-231 and MCF-7cells, transfection of COSMC reduced cellular Tn and STn occurrence and increased cell apoptosis [ 88 ]. These studies indicate that overexpression of C1GalT1 expression in cancer cells affects the expression and length of O-linked carbohydrate structures on cell death receptors and influences their response to cell death stimuli in cancer development.…”

Section: C1galt1 Is Overexpressed In Many Epithelial Cancers and Is Associated With Poorer Prognosis And Poorer Patient Survivalmentioning

confidence: 99%

Expression and Impact of C1GalT1 in Cancer Development and Progression

Wan

2021

Cancers

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C1GalT1 (T-synthase) is one of the key glycosyltransferases in the biosynthesis of O-linked mucin-type glycans of glycoproteins. It controls the formation of Core-1 disaccharide Galβ1,3GalNAcα- (Thomsen–Friedenreich oncofetal antigen, T or TF antigen) and Core-1-associated carbohydrate structures. Recent studies have shown that C1GalT1 is overexpressed in many cancers of epithelial origin including colon, breast, gastric, head and neck, pancreatic, esophageal, prostate, and hepatocellular cancer. Overexpression of C1GalT1 is often seen to also be associated with poorer prognosis and poorer patient survival. Change of C1GalT1 expression causes glycosylation changes of many cell membrane glycoproteins including mucin proteins, growth factor receptors, adhesion molecules, and death receptors. This leads to alteration of the interactions of these cell surface molecules with their binding ligands, resulting in changes of cancer cell activity and behaviors. This review summarizes our current understanding of the expression of C1GalT1 in various cancers and discusses the impact of C1GalT change on cancer cell activities in cancer development and progression.

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<p>Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens</p>

Cited by 8 publications

References 38 publications

Mucin-type sialyl-Tn antigen is associated with PD-L1 expression and predicts poor clinical prognosis in breast cancer

Mucin-type sialyl-Tn antigen is associated with PD-L1 expression and predicts poor clinical prognosis in breast cancer

Golgi Apparatus Regulates Plasma Membrane Composition and Function

Expression and Impact of C1GalT1 in Cancer Development and Progression

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