Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development

Iwaya, Takeshi; Sawada, Genta; Amano, Suburu; Kume, Kohei; Ito, Chie; Endo, Fumitaka; Konosu, Masafumi; Shioi, Yoshihiro; Akiyama, Yuji; Takahara, Taro; Otsuka, Koki; Nitta, Hiroyuki; Koeda, Keisuke; Morita, Masaru; Nishizuka, Satoshi; Sasaki, Akira; Mimori, Koshi

doi:10.3892/ijo.2016.3817

Cited by 8 publications

(8 citation statements)

References 24 publications

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“…ST6GALNAC1 encodes a sialyltransferase that acts as a catalyst for the synthesis of cancer-related sialyl-Tn (sTn) antigen critical for cell mobility [7]. It has been reported that ST6GALNAC1 was overexpressed in gastric, breast and prostate cancer cell lines, inducing sTn expression [8–11]. Previous findings have shown that ST6GALNAC1 played a part in elevating CSC phenotypes of colorectal cancer by activating the Akt signaling pathway [4].…”

Section: Introductionmentioning

confidence: 99%

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

et al. 2019

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Background Ovarian cancer is known as one of the most common cancers in the world among women. ST6GALNAC1 is highly expressed in cancer stem cells (CSCs), which correlates to high tumor-initiating, self-renewal and differentiation abilities. This present study aims to investigate how ST6GALNAC1 affects ovarian cancer stem cells (OCSCs). Methods In order to identify the differentially expressed genes related to ovarian cancer, microarray-based gene expression profiling of ovarian cancer was used, and ST6GALANC1 was one of the identified targets. After that, levels of ST6GALNAC1 in OCSCs and ovarian cancer cells were examined. Subsequently, an Akt signaling pathway inhibitor LY294002 was introduced into the cluster of differentiation 90 + (CD90 + ) stem cells, and cell proliferation, migration and invasion, levels of CXCL16, EGFR, CD44, Nanog and Oct4, as well as tumorigenicity of OCSCs were examined. Results By using a comprehensive microarray analysis, it was determined that ST6GALNAC1 was highly expressed in ovarian cancer and it regulated the Akt signaling pathway. High levels of ST6GALNAC1 were observed in OCSCs and ovarian cancer cells. Silencing ST6GALNAC1 was shown to be able to reduce cell proliferation, migration, invasion, self-renewal ability, tumorigenicity of OCSCs. In accordance with these results, the effects of ST6GALNAC1 in OCSCs were dependent on the Akt signaling pathway. Conclusions When taken together, our findings defined the potential stimulative roles of ST6GALNAC1 in ovarian cancer and OCSCs, which relied on the Akt signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

et al. 2019

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“…(Manual review of the publication revealed paracancerous normal tissues as the reference.) Similarly, ST6GALNAC1 was identified to be downregulated in ESCC (Iwaya et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of glycosyltransferases identified through comprehensive pan-cancer analysis

Vora

Cauley

et al. 2021

Preprint

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Despite accumulating evidence supporting a role for glycosylation in cancer progression and prognosis, the complexity of the human glycome and glycoproteome poses many challenges to understanding glycosylation-related events in cancer. In this study, a multifaceted genomics approach was applied to analyze the impact of differential expression of glycosyltransferases (GTs) in 16 cancers. An enzyme list was compiled and curated from numerous resources to create a consensus set of GTs. Resulting enzymes were analyzed for differential expression in cancer, and findings were integrated with experimental evidence from other analyses, including: similarity of healthy expression patterns across orthologous genes, miRNA expression, automatically-mined literature, curation of known cancer biomarkers, N-glycosylation impact, and survival analysis. The resulting list of GTs comprises 222 human enzymes based on annotations from five databases, 84 of which were differentially expressed in more than five cancers, and 14 of which were observed with the same direction of expression change across all implicated cancers. 25 high-value GT candidates were identified by cross-referencing multimodal analysis results, including PYGM, FUT6 and additional fucosyltransferases, several UDP-glucuronosyltransferases, and others, and are suggested for prioritization in future cancer biomarker studies. Relevant findings are available through OncoMX at https://data.oncomx.org, and the overarching pipeline can be used as a framework for similarly analysis across diverse evidence types in cancer. This work is expected to improve the understanding of glycosylation in cancer by transparently defining the space of glycosyltransferase enzymes and harmonizing variable experimental data to enable improved generation of data-driven cancer biomarker hypotheses.

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“…For example, ST6GALNAC1 expression in the IA sac was significantly positively correlated with IA size. ST6GALNAC1 encodes a sialyltransferase involved in protein glycosylation and is activated by CCL17 through the NF-kB pathway signaling [58][59][60]. TIFAB, which encodes a regulator of TRAF proteins that transduce extracellular inflammatory signals that mediate the NF-kB pathway, was also positively correlated with aneurysm size (and with IA wall enhancement, albeit not significantly) [61,62].…”

Section: Discussionmentioning

confidence: 99%

Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms

Tutino

Ishii

et al. 2021

Diagnostics

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The rupture of an intracranial aneurysm (IA) causes devastating hemorrhagic strokes. Yet, most IAs remain asymptomatic and undetected until they rupture. In the search for circulating biomarkers of unruptured IAs, we previously performed transcriptome profiling on whole blood and identified an IA-associated panel of 18 genes. In this study, we seek to determine if these genes are also differentially expressed within the IA lumen, which could provide a mechanistic link between the disease and the observed circulating gene expression patterns. To this end, we collected blood from the lumen of 37 IAs and their proximal parent vessels in 31 patients. The expression levels of 18 genes in the lumen and proximal vessel were then measured by quantitative polymerase chain reaction. This analysis revealed that the expression of 6/18 genes (CBWD6, MT2A, MZT2B, PIM3, SLC37A3, and TNFRSF4) was significantly higher in intraluminal blood, while the expression of 3/18 genes (ST6GALNAC1, TCN2, and UFSP1) was significantly lower. There was a significant, positive correlation between intraluminal and proximal expression of CXCL10, MT2A, and MZT2B, suggesting local increases of these genes is reflected in the periphery. Expression of ST6GALNAC1 and TIFAB was significantly positively correlated with IA size, while expression of CCDC85B was significantly positively correlated with IA enhancement on post-contrast MRI, a metric of IA instability and risk. In conclusion, intraluminal expression differences in half of the IA-associated genes observed in this study provide evidence for IA tissue-mediated transcriptional changes in whole blood. Additionally, some genes may be informative in assessing IA risk, as their intraluminal expression was correlated to IA size and aneurysmal wall enhancement.

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Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development

Cited by 8 publications

References 24 publications

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway

Differential expression of glycosyltransferases identified through comprehensive pan-cancer analysis

Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms

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