Transforming growth factor-β challenge alters the N-, O-, and glycosphingolipid glycomes in PaTu-S pancreatic adenocarcinoma cells

Zhang, Jing; Zhang, Zejian; Holst, Stephanie; Blöchl, Constantin; Madunić, Katarina; Wuhrer, Manfred; Dijke, Peter ten; Zhang, Tao

doi:10.1016/j.jbc.2022.101717

Cited by 5 publications

(5 citation statements)

References 107 publications

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“…Importantly, the results presented in this report support that alterations in GSL composition, including aberrant glycosylation, sialylation, and/or fucosylation, are an integral part of malignant transformation and tumor progression ( 6 , 22 , 27 , 32 , 46 , 75 , 79 , 80 , 81 , 82 ). Interestingly, striking differences in fucosylation, representing one of the most important oligosaccharide modifications linked to cancer, have been previously reported in cell lines ( 81 , 83 ) and tumor tissues ( 79 , 80 ) and therefore appear to be a promising target for cancer diagnosis and therapy ( 84 ).…”

Section: Discussionsupporting

confidence: 74%

Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

Hořejší¹,

Jin²,

Vaňková³

et al. 2023

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 74%

Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

Hořejší¹,

Jin²,

Vaňková³

et al. 2023

Journal of Biological Chemistry

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“…SB431542, a specific inhibitor of the TGFβ receptor, was configured according to the manufacturer's instructions. According to the results of previous studies 12,13 and preliminary experiments, 10 μM SB431542 was applied to cells and 2 h incubation was complished.…”

Section: Cell Culturementioning

confidence: 99%

Poly‐L‐Lactic acid increases collagen gene expression and synthesis in cultured dermal fibroblast (Hs68) through the TGF‐β/Smad pathway

Zhu

Dong

2022

J of Cosmetic Dermatology

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Objective: Poly-L-Lactic Acid (PLLA) is a synthetic polymer which possesses biocompatible and biodegradable properties, and is widely used in the clinical filler material.This study focuses on the potential role of PLLA on the collagen production of dermal fibroblasts and its mechanism. Methods:The dermal fibroblast Hs60 was treated with different concentration of PLLA. RT-qPCR was conducted for the determination of mRNA levels of collagen type I (COL1) alpha 1 (COL1A1), COL1 alpha 2 (COL1A2), elastin, matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2. Procollagen Type I C-peptide (PIP) enzyme immunoassay (EIA) Kit assay was carried out to analyze procollagen production. Western Blot was employed to examine the effect of PLLA and transforming frown factor (TGFβ) receptor-specific inhibitor (SB431542) on protein levels of COL1A1 and TGFβ/Smad signaling pathway related proteins.Results: With the increase of PLLA concentration, the production of procollagen gradually increased, and both protein and mRNA levels of COL1A1 and COL1A2 gradually increased (p < 0.001). Elevated PLLA concentrations increased elastin, TIMP-1, and TIMP-2 levels and attenuated MMP-1 expression. PLLA increased TGFβ levels in a dose-dependently manner. p-Smad2 and p-Smad3 protein levels were also increased by PLLA, but the influences were reversed by SB431542 (p < 0.001). Similarly, increased levels of COL1A1, COL1A2, TIMP-1, and TIMP-2 caused by PLLA were significantly inhibited by SB431542, whereas MMP-1 was typically elevated (p < 0.001). Conclusion:Poly-L-Lactic Acid promotes the collagen production of dermal fibroblasts by activating the TGFβ/Smad signaling pathway. The findings may lay a foundation for clinical material applications of PLLA.

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“…HCD was performed with an energy of 27% ± 5%, applying a 20-s dynamic exclusion window. Extraction of GSL and analysis of GSL-glycan alditols were performed in triplicate as previously described ( Zhang et al 2020 , 2022 ). In brief, GSLs were extracted and purified from ~1 × 10 6 cells.…”

Section: Methodsmentioning

confidence: 99%

“…MS spectra were acquired within an m/z range of 340–1,850 for GSL-glycans in enhanced mode using smart parameter setting (SPS) was set to m/z 900. Glycan structures were assigned on the basis of the known MS/MS fragmentation patterns in negative-ion mode ( Anugraham et al 2015 ; Zhang et al 2020 , 2022 ), elution order, and general glycobiological knowledge. Data analyses and structural annotation were performed as described previously ( de Haan et al 2022 ).…”

Section: Methodsmentioning

confidence: 99%

CRISPR-screen identifies ZIP9 and dysregulated Zn2+ homeostasis as a cause of cancer-associated changes in glycosylation

et al. 2023

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In epithelial cancers, truncated O-glycans, such as the Thomson-nouveau antigen (Tn) and its sialylated form (STn), are up-regulated on the cell surface and associated with poor prognosis and immunological escape. Recent studies have shown that these carbohydrate epitopes facilitate cancer development and can be targeted therapeutically; however, the mechanism underpinning their expression remains unclear. To identify genes directly influencing the expression of cancer-associated O-glycans, we conducted an unbiased, positive-selection, whole genome CRISPR knockout-screen using monoclonal antibodies against Tn and STn. We show that knockout of the Zn2+-transporter SLC39A9 (ZIP9), alongside the well-described targets C1GALT1 (C1GalT1) and its molecular chaperone, C1GALT1C1 (COSMC), results in surface-expression of cancer-associated O-glycans. No other gene perturbations were found to reliably induce O-glycan truncation. We furthermore show that ZIP9 knockout affects N-linked glycosylation, resulting in up-regulation of oligo-mannose, hybrid-type, and α2,6-sialylated structures as well as down-regulation of tri- and tetra-antennary structures. Finally, we demonstrate that accumulation of Zn2+ in the secretory pathway coincides with cell-surface presentation of truncated O-glycans in cancer tissue, and that over-expression of COSMC mitigates such changes. Collectively, the findings show that dysregulation of ZIP9 and Zn2+ induces cancer-like glycosylation on the cell surface by affecting the glycosylation machinery.

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Transforming growth factor-β challenge alters the N-, O-, and glycosphingolipid glycomes in PaTu-S pancreatic adenocarcinoma cells

Cited by 5 publications

References 107 publications

Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

Comprehensive characterization of complex glycosphingolipids in human pancreatic cancer tissues

Poly‐L‐Lactic acid increases collagen gene expression and synthesis in cultured dermal fibroblast (Hs68) through the TGF‐β/Smad pathway

CRISPR-screen identifies ZIP9 and dysregulated Zn2+ homeostasis as a cause of cancer-associated changes in glycosylation

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