Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

Oliveira‐Ferrer, Leticia; Hessling, Alexander von; Trillsch, Fabian; Mahner, Sven; Milde‐Langosch, Karin

doi:10.1007/s13277-015-3652-3

Cited by 35 publications

(25 citation statements)

References 33 publications

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“…Intense expression of oversulfated CS-GAGs was associated with poor prognosis in ovarian cancer [13]. Consistently, CHST11 expression has been suggested as an unfavorable prognostic factor in ovarian cancer [14]. High expression of CHST11 in colorectal cancer cell lines was linked to mesenchymal phenotype [15].…”

Section: Introductionmentioning

confidence: 74%

Carbohydrate (Chondroitin 4) Sulfotransferase-11-Mediated Induction of Epithelial-Mesenchymal Transition and Generation of Cancer Stem Cells

Behrens¹,

Jousheghany²,

Yao-Borengasser³

et al. 2020

Pharmacology

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Introduction:We have previously shown that the expression of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) is elevated in human breast cancer tissues, and that its expression in human breast cancer cell lines is associated with aggressive behavior of cells. The clinical significance of CHST11 expression is unknown, and its function in breast cancer cells is not fully understood. Objective: The current study was performed to define the clinical significance of this gene and address its biological function in promoting the aggressive behavior of breast cancer cells. Methods: Publicly available datasets were analyzed to determine the correlation of CHST11 expression with breast cancer survival. MCF-7 cells were transfected with the human CHST11 gene, and MCF-7-CHST11 cells with stable expression of the gene were established. Morphology and metastatic capacity of transfected cells were monitored in vitro. E-cadherin and β-catenin expression was compared by immunofluorescence. The expression of genes involved in epithelial-mesen-chymal transition (EMT) and pluripotency was determined using real-time PCR. The Wnt inhibitor, Wnt-C59, was used to examine the involvement of Wnt in CHST11-mediated morphology. Results: The elevated expression of CHST11 in breast tumor specimens was significantly associated with poor survival among patients. MCF-7-CHST11 cells displayed morphological characteristics consistent with EMT, together with a significantly higher proliferation rate, enhanced migratory potential, and more robust anchorage-independent growth. MCF-7-CHST11 cells showed decreased expression of E-cadherin and increased accumulation of β-catenin, as assessed by immunofluorescence. Consistently, increased expression of CHST11 resulted in upregulation of key EMT and stem cell markers. Morphological transition in MCF-7-CHST11 cells was partially reversed by co-incubation with an inhibitor of the Wnt pathway. Conclusions: Our findings support a role for CHST11 in induction of EMT and stem celllike properties. Our data also associate the expression levels of CHST11 in breast tumor specimens with patients' survival. The results have a significant implication for CHST11 expression level as a novel molecular signature for predictive and prognostic purposes in breast cancer. Moreover, with a possible role in driving tumor cell aggressiveness, CHST11 expression might be further considered as a potential therapeutic target for breast cancer.

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Section: Introductionmentioning

confidence: 74%

Carbohydrate (Chondroitin 4) Sulfotransferase-11-Mediated Induction of Epithelial-Mesenchymal Transition and Generation of Cancer Stem Cells

Behrens¹,

Jousheghany²,

Yao-Borengasser³

et al. 2020

Pharmacology

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“…Two sulfotransferases, CHST11/C4ST1 and CHST13/C4ST3, are known to be able to produce chondroitin‐4‐sulfate of glucuronic acid‐N‐acetylgalactosamine disaccharides (the sulfotransferases CHST12/C4ST2 and CHST14/D4ST1 prefer iduronic acid‐containing disaccharides of dermatan as substrate) . CHST15/GalNAc4S‐6ST is the only enzyme subsequently catalyzing the sulfation of chondroitin sulfate 4‐sulfate to form the disulfated isoform of chondroitin sulfate 4,6‐sulfate (CHST3/C6ST1 and CHST7/C6ST2 mainly catalyze sulfation of the 6‐hydroxyl group of the chondroitin sulfate backbone to form the CS‐C isoform of chondroitin 6‐sulfate) . Thus, CHST15 may have a unique role in modulating the context of extracellular glycosaminoglycans.…”

Section: Discussionmentioning

confidence: 99%

“…28 CHST15/ GalNAc4S-6ST is the only enzyme subsequently catalyzing the sulfation of chondroitin sulfate 4-sulfate to form the disulfated isoform of chondroitin sulfate 4,6-sulfate (CHST3/C6ST1 and CHST7/C6ST2 mainly catalyze sulfation of the 6-hydroxyl group of the chondroitin sulfate backbone to form the CS-C isoform of chondroitin 6-sulfate). 28,29 Thus, CHST15 may have a unique role in modulating the context of extracellular glycosaminoglycans. Our study provides molecular insights into the regulation of CHST15 expression in breast cancer cells and its functional consequence in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA HOTAIR promotes invasion of breast cancer cells through chondroitin sulfotransferase CHST15

Liu

Wang

Lin

et al. 2019

Intl Journal of Cancer

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The long noncoding RNA HOTAIR plays significant roles in promoting cancer metastasis. However, how it conveys an invasive advantage in cancer cells is not clear. Here we identify the chondroitin sulfotransferase CHST15 (GalNAc4S‐6ST) as a novel HOX transcript antisense intergenic RNA (HOTAIR) target gene using RNA profiling and show that CHST15 is required for HOTAIR‐mediated invasiveness in breast cancer cells. CHST15 catalyzes sulfation of the C6 hydroxyl group of the N‐acetyl galactosamine 4‐sulfate moiety in chondroitin sulfate to form the 4,6‐disulfated chondroitin sulfate variant known as the CS‐E isoform. We show that HOTAIR is necessary and sufficient for CHST15 transcript expression. Inhibition of CHST15 by RNA interference abolished cell invasion promoted by HOTAIR but not on HOTAIR‐mediated migratory activity. Conversely, reconstitution of CHST15 expression rescued the invasive activity of HOTAIR‐depleted cells. In corroboration with this mechanism, blocking cell surface chondroitin sulfate using a pan‐CS antibody or an antibody specifically recognizes the CS‐E isoform significantly suppressed HOTAIR‐induced invasion. Inhibition of CHST15 compromised tumorigenesis and metastasis in orthotopic breast cancer xenograft models. Furthermore, the expression of HOTAIR closely correlated with the level of CHST15 protein in primary as well as metastatic tumor lesions. Our results demonstrate a novel mechanism underlying the function of HOTAIR in tumor progression through programming the context of cell surface glycosaminoglycans. Our results further establish that the invasive and migratory activities downstream of HOTAIR are distinctly regulated, whereby CHST15 preferentially controls the arm of invasiveness. Thus, the HOTAIR‐CHST15 axis may provide a new avenue toward novel therapeutic strategies and prognosis biomarkers for advanced breast cancer.

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“…In a study of ovarian cancer, high expression of CHST11 at the protein level was independently associated with unfavorable progression-free survival. 20 Chondroitin sulfates also play a major role in breast cancer metastasis according to Cooney et al 21 The CHST11 gene was highly expressed in aggressive breast cancer cells and a positive correlation was found to P-selectin binding to cells.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic changes as prognostic predictors in endometrial carcinomas

2016

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Endometrial carcinoma is one of the most frequent gynecological malignancies of the female. The diagnostic and prognostic markers for the high-risk subgroups with unfavorable prognosis are under intense debate worldwide, and, therefore, the aim of this study was to identify new potential DNA methylation markers for the high-risk groups. We used the Illumina Infinium HumanMethylation450 BeadChip to analyze the DNA methylation pattern and investigated its association with clinicopathological features important for defining the high-risk (FIGO-grade 3) and low-risk (FIGO-grade 1) groups of patients with endometrial cancer (n D 31 and n D 39, respectively). We identified specific DNA methylation signature in high-risk endometrial tumors, and potential molecular biomarker genes (TBX2, CHST11, and NID2) associated with unfavorable clinical predictive and prognostic factors.

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Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer

Cited by 35 publications

References 33 publications

Carbohydrate (Chondroitin 4) Sulfotransferase-11-Mediated Induction of Epithelial-Mesenchymal Transition and Generation of Cancer Stem Cells

Carbohydrate (Chondroitin 4) Sulfotransferase-11-Mediated Induction of Epithelial-Mesenchymal Transition and Generation of Cancer Stem Cells

Long noncoding RNA HOTAIR promotes invasion of breast cancer cells through chondroitin sulfotransferase CHST15

Epigenetic changes as prognostic predictors in endometrial carcinomas

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