Core fucosylation of copper transporter 1 plays a crucial role in cisplatin‐resistance of epithelial ovarian cancer by regulating drug uptake

Lv, Xiaoxue; Song, Jing; Xue, Kai; Li, Zhi; Li, Ming; Zahid, Danishi; Cao, Hongyu; Wang, Lu; Song, Wanli; Ma, Tiantian; Gu, Jianguo; Li, Wenzhe

doi:10.1002/mc.22971

Cited by 29 publications

(15 citation statements)

References 42 publications

(203 reference statements)

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“…Increased core fucosylation is involved with the development of several malignant tumors and is linked to the severity of cancers [4–8]. In the process of epithelial‐mesenchymal transformation of NSCLC, deletion of E‐cadherin can increase the expression of β‐catenin protein, which in turn binds to the lymphatic enhancer binding factor‐1 (LEF‐1)/T cell factor site on the Fut8 promoter and results in upregulation of protein core fucosylation [26].…”

Section: Discussionmentioning

confidence: 99%

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Loss of core fucosylation enhances the anticancer activity of cytotoxic T lymphocytes by increasing PD‐1 degradation

Zhang

et al. 2020

Eur J Immunol

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As an immune checkpoint, programmed cell death 1 (PD‐1) and its ligand (PD‐L1) pathway plays a crucial role in CD8+ cytotoxic T lymphocytes (CTL) activation and provides antitumor responses. The N‐glycans of PD‐1 and PD‐L1 are highly core fucosylated, which are solely catalyzed by the core fucosyltransferase (Fut8). However, the precise biological mechanisms underlying effects of core fucosylation of PD‐1 and PD‐L1 on CTL activation have not been fully understood. In this study, we found that core fucosylation was significantly upregulated in lung adenocarcinoma. Compared to those of Fut8+/+OT‐I mice, the lung adenocarcinoma formation induced by urethane was markedly reduced in Fut8−/−OT‐I mice. De‐core fucosylation of PD‐1 compromised its expression on Fut8−/− CTL, resulted in enhanced Fut8−/− CTL activation and cytotoxicity, leading to more efficient tumor eradication. Indeed, loss of core fucosylation significantly enhanced the PD‐1 ubiquitination and in turn led to the degradation of PD‐1 in the proteasome. Our current work indicates that inhibition of core fucosylation is a unique strategy to reduce PD‐1 expression for the antilung adenocarcinoma immune therapy in the future.

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Section: Discussionmentioning

confidence: 99%

“…1A) [3]. The high expression of Fut8 was found to be associated with an unfavorable clinical outcome in hepatocellular carcinoma, prostate cancer, melanoma, ovarian cancer, NSCLC, and breast cancer [4–8].…”

Section: Introductionmentioning

confidence: 99%

Loss of core fucosylation enhances the anticancer activity of cytotoxic T lymphocytes by increasing PD‐1 degradation

Zhang

et al. 2020

Eur J Immunol

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“…This could also be related to a higher migration capacity and may lead to the establishment of a metastatic tumor. Additionally, high fucosylation in OVCAR-3 could be an important feature that confers resistance to cisplatin [66,67].…”

Section: Discussionmentioning

confidence: 99%

Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins

Alberto-Aguilar

Hernández‐Ramírez

Osorio-Trujillo

et al. 2019

Cancer Microenvironment

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Ovarian cancer is considered to be the most lethal type of gynecological cancer. During the advanced stages of ovarian cancer, an accumulation of ascites is observed. Fucosylation has been classified as an abnormal post-translational modification that is present in many diseases, including ovarian cancer. Ovarian cancer cells that are cultured with ascites stimulation change their morphology; concomitantly, the fucosylation process is altered. However, it is not known which fucosylated proteins are modified. The goal of this work was to identify the differentially fucosylated proteins that are expressed by ovarian cancer cell lines that are cultured with ovarian cancer patients' ascites. Aleuria aurantia lectin was used to detect fucosylation, and some changes were observed, especially in the cell membrane. Affinity chromatography and mass spectrometry (MALDI-TOF) were used to identify 6 fucosylated proteins. Four proteins (Intermediate filament family orphan 1 [IFFO1], PHD finger protein 20-like protein 1 [PHF20L1], immunoglobulin gamma 1 heavy chain variable region partial [IGHV1-2], and Zinc finger protein 224 [ZNF224]) were obtained from cell cultures stimulated with ascites, and the other two proteins (Peregrin [BRPF1] and Dystrobrevin alpha [DTNA]) were obtained under normal culture conditions. The fucosylated state of some of these proteins was further analyzed. The experimental results show that the ascites of ovarian cancer patients modulated the fucosylation process. The PHD finger protein 20-like protein 1, Zinc finger protein 224 and Peregrin proteins colocalize with fucosylation at different levels.

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“…Another enzyme involved in drug resistance (to cisplatin) is core fucosyltransferase (FUT8) 15 . One of the core‐fucosylated proteins was copper transporter 1 (CTR1), an important transporter in regulating the uptake of cisplatin, and such a glycan modification of the transporter protein suppressed cisplatin uptake into the cells 16 . An enhanced level of FUT8 was also linked to radio‐resistance and a poor prognosis in oesophageal squamous cell carcinoma patients with identification of CD147 protein as being core‐fucosylated 17 .…”

Section: Introductionmentioning

confidence: 99%

Glycan signatures for the identification of cisplatin‐resistant testicular cancer cell lines: Specific glycoprofiling of human chorionic gonadotropin (hCG)

et al. 2022

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Background Testicular cancer (TC) is the most frequent type of cancer among young men aged between 15 and 34 years. TC is treated using cisplatin, but 3%–5% of TC patients fail to respond to cisplatin, with a very bad to fatal prognosis. Accordingly, it is most important to quickly and readily identify those TC patients who are resistant to cisplatin treatment. Methods This study seeks to investigate changes in the glycosylation associated with cisplatin resistance to TC cell lines. Results A specific glycoprofiling of human chorionic gonadotropin (hCG) was analysed in three TC cell lines and one cell line of female origin. A typical calibration curve for hCG glycoprofiling showed a dynamic range up to 50 ng/ml, with a limit of detection of 0.3 ng/ml and assay reproducibility represented by relative standard deviation of 3.0%. Changes in the glycan signatures on hCG were analysed in cisplatin‐sensitive cell lines and in their cisplatin‐resistant sub‐lines using an enzyme‐linked lectin assay (ELLA) protocol. An immobilised antibody was applied to a selective capture of hCG from a cytoplasmic fraction of cell lysates with final incubation using a lectin from a panel of 17 lectins. Conclusion The results suggest that one particular lectin Dolichos biflorus agglutinin (DBA) can selectively discriminate sensitive TC cell lines from resistant TC cell lines. Moreover, there are additional lectins which can provide useful information about the strength of cisplatin resistance.

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Core fucosylation of copper transporter 1 plays a crucial role in cisplatin‐resistance of epithelial ovarian cancer by regulating drug uptake

Cited by 29 publications

References 42 publications

Loss of core fucosylation enhances the anticancer activity of cytotoxic T lymphocytes by increasing PD‐1 degradation

Loss of core fucosylation enhances the anticancer activity of cytotoxic T lymphocytes by increasing PD‐1 degradation

Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins

Glycan signatures for the identification of cisplatin‐resistant testicular cancer cell lines: Specific glycoprofiling of human chorionic gonadotropin (hCG)

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