Alpha-(1,6)-fucosyltransferase (FUT8) affects the survival strategy of osteosarcoma by remodeling TNF/NF-κB2 signaling

Lin, Shanyi; Zhou, Lenian; Dong, Yang; Yang, Qingcheng; Yang, Quanjun; Jin, Hanqiang; Tan, Yuan; Zhou, Shumin

doi:10.1038/s41419-021-04416-x

Cited by 14 publications

(8 citation statements)

References 43 publications

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“…Consequently, modulation of apoptosis sensitivity during early carcinogenesis might be a viable treatment strategy for CRC that is worthy of investigation to address core fucosylated glycan intermediates involved in apoptosis and drug resistance. In this regard, reduced core fucosylation of TNF receptors may be mechanistically linked to decreased mitochondrial-dependent apoptosis because of the activation of the non-canonical NF-B pathway, as recently reported in osteosarcoma 75 . Therefore, targeting key (1,6)fucosylated proteins could strengthen the panoply of treatment alternatives for CRC and other neoplasias characterised by exacerbated core fucosylation 76,77 .…”

Section: Discussionmentioning

confidence: 52%

Core Fucosylation Mediated by the FucT-8 Enzyme Affects Trail-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells

López-Cortés¹,

Pardo²,

Muinelo‐Romay³

et al. 2023

Preprint

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Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the (1,6)fucose residue to the pentasaccharide core of complex N-glycans. Specifically, in the cellular model of colorectal cancer (CRC) progression formed using the human syngeneic lines SW480 and SW620, knockdown of the FucT-8-encoding FUT8 gene significantly enhanced TRAIL-induced apoptosis in SW480 cells. However, FUT8 repression did not affect SW620 cells, which suggests that core fucosylation differentiates TRAIL-sensitive premetastatic SW480 cells from TRAIL-resistant metastatic SW620 cells. In this regard, we provide evidence that phosphorylation of ERK1/2 kinases can dynamically regulate TRAIL-dependent apoptosis and that core fucosylation can control the ERK/MAPK pro-survival pathway in which SW480 and SW620 cells participate. Moreover, the depletion of core fucosylation sensitises primary tumour SW480 cells to the combination of TRAIL and low doses of 5-FU, oxaliplatin, irinotecan or mitomycin C. In contrast, combination of TRAIL and oxaliplatin, irinotecan or bevacizumab reinforces resistance of FUT8-knockdown metastatic SW620 cells to apoptosis. Consequently, FucT-8 could be a plausible target for increasing apoptosis and drug response in early CRC.

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Section: Discussionmentioning

confidence: 52%

Core Fucosylation Mediated by the FucT-8 Enzyme Affects Trail-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells

López-Cortés¹,

Pardo²,

Muinelo‐Romay³

et al. 2023

Preprint

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“…In addition, Lin et al demonstrated that fucosyltransferase 8 (FUT8) influences OS survival by regulating the core fucosylation levels of TNF receptors (TNFRs). Decreased fucosylation of TNFRs activates the non-canonical NF-

B signaling pathway, ultimately reducing mitochondria-dependent apoptosis in OS cells [ 50 ]. The contradictory results regarding the expression of these TNFRSF1A genes may be related to tissue specificity and age range.…”

Section: Discussionmentioning

confidence: 99%

Identification of TNFRSF1A as a potential biomarker for osteosarcoma

Zhang,

Liu,

Wang

2024

CBM

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BACKGROUND: Osteosarcoma (OS) is a relatively rare malignant bone tumor in teenagers; however, its molecular mechanisms are not yet understood comprehensively. OBJECTIVE: The study aimed to use necroptosis-related genes (NRGs) and their relationships with immune-related genes to construct a prognostic signature for OS. METHODS: TARGET-OS was used as the training dataset, and GSE 16091 and GSE 21257 were used as the validation datasets. Univariate regression, survival analysis, and Kaplan-Meier curves were used to screen for hub genes. The immune-related targets were screened using immune infiltration assays and immune checkpoints. The results were validated using nomogram and decision curve analyses (DCA). RESULTS: Using univariate Cox regression analysis, TNFRSF1A was screened from 14 NRGs as an OS prognostic signature. Functional enrichment was analyzed based on the median expression of TNFRSF1A. The prognosis of the TNFRSF1A low-expression group in the Kaplan-Meier curve was notably worse. Immunohistochemistry analysis showed that the number of activated T cells and tumor purity increased considerably. Furthermore, the immune checkpoint lymphocyte activation gene 3 (LAG-3) is a possible target for intervention. The nomogram accurately predicted 1-, 3-, and 5-year survival rates. DCA validated the model (C = 0.669). Conclusion: TNFRSF1A can be used to elucidate the potential relationship between the immune microenvironment and NRGs in OS pathogenesis.

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“…However, FUT8 was found to be expressed at lower levels in osteosarcoma, leading to lower core fucosylation levels of TNF receptors. Lower fucosylation of TNF receptors decreased mitochondria-dependent apoptosis by activating NF-κB2 signalling [ 37 ]. Interestingly, our study revealed that FUT8 was upregulated in OC tissues but was a good prognostic factor.…”

Section: Discussionmentioning

confidence: 99%

A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer

Jia

et al. 2023

J Ovarian Res

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Background Ovarian cancer (OC) is the most fatal gynaecological malignancy and has a poor prognosis. Glycosylation, the biosynthetic process that depends on specific glycosyltransferases (GTs), has recently attracted increasing importance due to the vital role it plays in cancer. In this study, we aimed to determine whether OC patients could be stratified by glycosyltransferase gene profiles to better predict the prognosis and efficiency of immune checkpoint blockade therapies (ICBs). Methods We retrieved transcriptome data across 420 OC and 88 normal tissue samples using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively. An external validation dataset containing 185 OC samples was downloaded from the Gene Expression Omnibus (GEO) database. Knockdown and pathway prediction of B4GALT5 were conducted to investigate the function and mechanism of B4GALT5 in OC proliferation, migration and invasion. Results A total of 50 differentially expressed GT genes were identified between OC and normal ovarian tissues. Two clusters were stratified by operating consensus clustering, but no significant prognostic value was observed. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 6-gene signature was built that classified OC patients in the TCGA cohort into a low- or high-risk group. Patients with high scores had a worse prognosis than those with low scores. This risk signature was further validated in an external GEO dataset. Furthermore, the risk score was an independent risk predictor, and a nomogram was created to improve the accuracy of prognostic classification. Notably, the low-risk OC patients exhibited a higher degree of antitumor immune cell infiltration and a superior response to ICBs. B4GALT5, one of six hub genes, was identified as a regulator of proliferation, migration and invasion in OC. Conclusion Taken together, we established a reliable GT-gene-based signature to predict prognosis, immune status and identify OC patients who would benefit from ICBs. GT genes might be a promising biomarker for OC progression and a potential therapeutic target for OC.

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Alpha-(1,6)-fucosyltransferase (FUT8) affects the survival strategy of osteosarcoma by remodeling TNF/NF-κB2 signaling

Cited by 14 publications

References 43 publications

Core Fucosylation Mediated by the FucT-8 Enzyme Affects Trail-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells

Core Fucosylation Mediated by the FucT-8 Enzyme Affects Trail-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells

Identification of TNFRSF1A as a potential biomarker for osteosarcoma

A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer

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