Sox2 promotes expression of the ST6Gal-I glycosyltransferase in ovarian cancer cells

Dorsett, Kaitlyn A.; Jones, Robert B.; Ankenbauer, Katherine E; Hjelmeland, Anita B.; Bellis, Susan L.

doi:10.1186/s13048-019-0574-5

Cited by 40 publications

(27 citation statements)

References 92 publications

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“…SOX2 has been involved in numerous cancers, such as prostate cancer, ovarian cancer, and breast cancer. 25 , 26 , 27 Concurred with our results, a prior study indicated SOX2 upregulation in EC samples and that SOX2 overexpression enhanced EC cell proliferation and invasion. 28 Meanwhile, a study by Ishida et al.…”

Section: Discussionsupporting

confidence: 88%

SOX2-Upregulated microRNA-30e Promotes the Progression of Esophageal Cancer via Regulation of the USP4/SMAD4/CK2 Axis

Yang

Fan

Ren

et al. 2021

Molecular Therapy - Nucleic Acids

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Esophageal cancer (EC) is a highly aggressive disease, and its progression involves a complex gene regulation network. Transcription factor SOX2 is amplified in various cancers including EC. A pathway involving SOX2 regulation of microRNAs (miRNAs) and their target genes has been previously revealed. This study aims to delineate the ability of SOX2 to influence the EC progression, with the involvement of miR-30e/USP4/SMAD4/CK2 axis. SOX2 expression was first examined in the clinical tissue samples from 30 EC patients. Effects of SOX2 on proliferation, migration, and invasion alongside tumorigenicity of transfected cells were examined by means of gain- and loss-of-function experiments. EC tissues and cells exhibited high expression of SOX2, miR-30e, and CK2 and poor expression of USP4 and SMAD4. Mechanistically, SOX2 was positively correlated with miR-30e and upregulated the expression of miR-30e. miR-30e specifically targeted USP4, which induced deubiquitination of SMAD4 and promoted its expression. Meanwhile, SMAD4 was enriched in the CK2 promoter region and thus inhibited its expression. SOX2 stimulated EC cell proliferative, invasive, and migratory capacities in vitro and tumor growth in vivo by regulating the miR-30e/USP4/SMAD4/CK2 axis. Collectively, our work reveals a novel SOX2-mediated regulatory network in EC that may be a viable target for EC treatment.

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Section: Discussionsupporting

confidence: 88%

SOX2-Upregulated microRNA-30e Promotes the Progression of Esophageal Cancer via Regulation of the USP4/SMAD4/CK2 Axis

Yang

Fan

Ren

et al. 2021

Molecular Therapy - Nucleic Acids

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“… 22 Hypersialylation is associated with, and suggested to be causal to, increased aggressiveness, stemness, resistance to chemotherapeutic agents, ability to survive in stressful conditions like hypoxia, and impaired nutrient supply. 24 , 25 , 27 , 41 However, when we performed flow cytometry to isolate the two subpopulations showing distinct α2,6-sialic acid levels, the one showing lower levels (which we denoted as medium 2,6-Sial cells) showed greater invasion than high 2,6-Sial cells both in the transwell assay and in 3D cultures. Medium 2,6-Sial cells were also observed to adhere better to both laminin-rich and collagenous ECM, as well as migrate through the latter with higher velocity compared to high 2,6-Sial cells.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in 2,6-Linked Sialic Acids Potentiates Invasion of Breast Cancer Epithelia

et al. 2021

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Heterogeneity in phenotypes of malignantly transformed cells and aberrant glycan expression on their surface are two prominent hallmarks of cancers that have hitherto not been linked to each other. In this paper, we identify differential levels of a specific glycan linkage: α2,6-linked sialic acids within breast cancer cells in vivo and in culture. Upon sorting out two populations with moderate, and relatively higher, cell surface α2,6-linked sialic acid levels from the triple-negative breast cancer cell line MDA-MB-231, both populations (denoted as medium and high 2,6-Sial cells, respectively) stably retained their levels in early passages. Upon continuous culturing, medium 2,6-Sial cells recapitulated the heterogeneity of the unsorted line whereas high 2,6-Sial cells showed no such tendency. Compared with high 2,6-Sial cells, the medium 2,6-Sial counterparts showed greater adhesion to reconstituted extracellular matrices (ECMs) and invaded faster as single cells. The level of α2,6-linked sialic acids in the two sublines was found to be consistent with the expression of a specific glycosyl transferase, ST6GAL1. Stably knocking down ST6GAL1 in the high 2,6-Sial cells enhanced their invasiveness. When cultured together, medium 2,6-Sial cells differentially migrated to the edge of growing tumoroid-like cocultures, whereas high 2,6-Sial cells formed the central bulk. Multiscale simulations in a Cellular Potts model-based computational environment calibrated to our experimental findings suggest that differential levels of cell–ECM adhesion, likely regulated by α2,6-linked sialic acids, facilitate niches of highly invasive cells to efficiently migrate centrifugally as the invasive front of a malignant breast tumor.

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“…The pathogenesis of SOC is a complex process that is driven by specific genetic and epigenetic alterations. For example, elevated ST6GAL1 expression and hypermethylation of RASSF1A have been demonstrated to play critical roles in ovarian cancer (20,21). The present study aimed to identify the core genes and significant gene sets for SOC to improve the understanding of the potential molecular mechanisms, which may help develop novel biomarkers or therapeutic targets for this disease.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of core genes for serous ovarian adenocarcinoma via bioinformatics analysis

et al. 2020

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Ovarian cancer is a fatal gynaecological malignancy in women worldwide, and serous ovarian cancer (SOC) is considered the most common histological subtype of this malignancy. Thus, the present study aimed to identify the core genes for SOC via bioinformatics analysis. The GSE18520 and GSE14407 datasets were downloaded from the Gene Expression Omnibus (GEO) database to screen for differentially expressed genes (DEGs) and perform gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was constructed to identify the core genes, while The Cancer Genome Atlas (TCGA) database was used to screen for prognosis-associated DEGs. Furthermore, clinical samples were collected for further validation of kinesin family member 11 (KIF11) gene. In the GEO analysis, a total of 198 DEGs were identified, including 81 upregulated and 117 downregulated genes compared SOC to normal tissue. GSEA across the two datasets demonstrated that 16 gene sets, including those involved in the cell cycle and DNA replication, were notably associated with SOC. A PPI network of the DEGs was constructed with 130 nodes and 387 edges. Subsequently, 20 core genes involved in the same top-ranked module were filtered out by submodule analysis. Survival analysis identified three predictive genes for SOC prognosis, including KIF11, CLDN3 and FGF13. KIF11 was identified as a core and predictive gene and thus was further validated using clinical samples. The results demonstrated that KIF11 was upregulated in tumour tissues compared with adjacent normal tissues and was associated with aggressive factors, including tumour grade, TNM stage and lymph node invasion. In conclusions, the present study identified the core genes and gene sets for SOC, thus extending the understanding of SOC occurrence and progression. Furthermore, KIF11 was identified as a promising tumour-promoting gene and a potential target for the diagnosis and treatment of SOC.

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Sox2 promotes expression of the ST6Gal-I glycosyltransferase in ovarian cancer cells

Cited by 40 publications

References 92 publications

SOX2-Upregulated microRNA-30e Promotes the Progression of Esophageal Cancer via Regulation of the USP4/SMAD4/CK2 Axis

SOX2-Upregulated microRNA-30e Promotes the Progression of Esophageal Cancer via Regulation of the USP4/SMAD4/CK2 Axis

Heterogeneity in 2,6-Linked Sialic Acids Potentiates Invasion of Breast Cancer Epithelia

Identification and validation of core genes for serous ovarian adenocarcinoma via bioinformatics analysis

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