A lectin-based glycomic approach identifies FUT8 as a driver of radioresistance in oesophageal squamous cell carcinoma

Shen, Li; Xia, Min; Deng, Xinzhou; Ke, Qing; Zhang, Chuanyi; Peng, Feng; Xiao, Dong; Luo, Zhiguo

doi:10.1007/s13402-020-00517-5

Cited by 22 publications

(19 citation statements)

References 50 publications

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“…As described previously [ 28 ], mice were grouped into no irradiation group (n = 4) or irradiation group (n = 4). Irradiation was given 20 days later.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells

et al. 2021

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Background Nasopharyngeal carcinoma (NPC) is a tumor deriving from nasopharyngeal epithelium. Peptidyl-arginine deiminase 4 (PAD4) is a vital mediator of histone citrullination and plays an essential role in regulating disease process. Radiotherapy is an essential method to treat NPC. In this research, we explored the effect of PAD4 on NPC radiosensitivity. Methods We enrolled 50 NPC patients, established mice xenograft model, and purchased cell lines for this study. Statistical analysis and a series of experiments including RT-qPCR, clonogenic survival, EdU, Transwell, and wound healing assays were done. Results Our data manifested that PAD4 (mRNA and protein) presented a high expression in NPC tissues and cells. GSK484, an inhibitor of PAD4, could inhibit activity of PAD4 in NPC cell lines. PAD4 overexpression promoted the radioresistance, survival, migration, and invasion of NPC cells, whereas treatment of GSK484 exerted inhibitory effects on radioresistance and aggressive phenotype of NPC cells. Additionally, GSK484 could attenuate the effect of PAD4 of NPC cell progression. More importantly, we found that GSK484 significantly inhibited tumor size, tumor weight and tumor volume in mice following irradiation. Conclusions PAD4 inhibitor GSK484 attenuated the radioresistance and cellular progression in NPC.

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“…As described previously [ 28 ], mice were grouped into no irradiation group (n = 4) or irradiation group (n = 4). Irradiation was given 20 days later.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells

et al. 2021

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“…2020 saw the publication of several pivotal studies focussing on novel FUT8 discoveries. Key publications have ranged from the first in depth description of FUT8’s structural basis [ 43 , 44 , 144 , 145 ], identification of FUT8’s substrate specificity [ 146 ], its regulatory role amongst various cancers [ 27 , 82 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ] and the inhibition of fucosylation [ 138 , 140 ]. The literature has vastly expanded upon our understanding and the particular importance of FUT8 in human disease.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer

Bastian

Scott

Elliott

et al. 2021

IJMS

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Aberrant glycosylation is a universal feature of cancer cells that can impact all steps in tumour progression from malignant transformation to metastasis and immune evasion. One key change in tumour glycosylation is altered core fucosylation. Core fucosylation is driven by fucosyltransferase 8 (FUT8), which catalyses the addition of α1,6-fucose to the innermost GlcNAc residue of N-glycans. FUT8 is frequently upregulated in cancer, and plays a critical role in immune evasion, antibody-dependent cellular cytotoxicity (ADCC), and the regulation of TGF-β, EGF, α3β1 integrin and E-Cadherin. Here, we summarise the role of FUT8 in various cancers (including lung, liver, colorectal, ovarian, prostate, breast, melanoma, thyroid, and pancreatic), discuss the potential mechanisms involved, and outline opportunities to exploit FUT8 as a critical factor in cancer therapeutics in the future.

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“…One week later, mice were treated with YW3‐56 (25 mg/kg daily for 35 days) or control (10% DMSO in PBS) by intraperitoneal injection. For tumor radiosensitivity study, as previously described, 21 the irradiation was given 20 days after tumor implantation. Briefly, the mice with YW3‐56 or DMSO were exposed to 8 Gy of irradiation.…”

Section: Animal Studymentioning

confidence: 99%

PAD4 inhibitor promotes DNA damage and radiosensitivity of nasopharyngeal carcinoma cells

Chen

Wei

Luo

et al. 2021

Environmental Toxicology

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Peptidylarginine deiminases 4 (PAD4), a kind of enzyme capable of converting protein arginine or mono‐methylarginine into citrulline, has been identified to display a key role in diverse diseases. Radiotherapy is frequently used in nasopharyngeal carcinoma (NPC) treatment and induces DNA double strand breaks. In this study, whether PAD4 inhibitor YW3‐56 affects the radiosensitivity of NPC cells was explored. RT‐qPCR, immunofluorescence, western blot, clonogenic survival, and flow cytometry assays were used to assess the function of PAD4 and YW3‐56 in NPC. We found the upregulation of PAD4 expression in NPC cells. PAD4 overexpression suppressed NPC cell apoptosis and promoted cell cycle, while PAD4 depletion had an opposite result. Moreover, the survival of NPC cells after irradiation was increased by overexpression of PAD4. PAD4 overexpression inhibited DNA damage and sensitivity of NPC cells to irradiation. Functional assays showed that YW3‐56 treatment promoted DNA damage, apoptosis, and radiosensitivity of NPC cells. Importantly, YW3‐56 treatment inhibited tumor growth in vivo. Overall, this study revealed the efficacy of PAD4 inhibitor YW3‐56 in promoting sensitivity of NPC cells to irradiation.

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A lectin-based glycomic approach identifies FUT8 as a driver of radioresistance in oesophageal squamous cell carcinoma

Cited by 22 publications

References 50 publications

Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells

Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells

FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer

PAD4 inhibitor promotes DNA damage and radiosensitivity of nasopharyngeal carcinoma cells

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