FUT6 inhibits the proliferation, migration, invasion, and EGF-induced EMT of head and neck squamous cell carcinoma (HNSCC) by regulating EGFR/ERK/STAT signaling pathway

Wang, Qian; Liao, Chengcheng; Tan, Zhangxue; Li, Xiaolan; Guan, Xiaoyan; Li, Hao; Tian, Zhongjia; Liu, Jian-Guo; An, Jiaxing

doi:10.1038/s41417-022-00530-w

Cited by 11 publications

(7 citation statements)

References 55 publications

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“…As reported, FUT6 is related to the occurrence and metastasis of gastric cancer [17] and colorectal cancer [18]. A recent study by [19] revealed that FUT6 suppresses the proliferation, migration, invasion, and EGF-induced epithelial-mesenchymal transition in HNSCC cells, which corroborated our ndings.…”

Section: Discussionsupporting

confidence: 92%

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma

Li,

Liu

et al. 2023

Preprint

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Background Head and neck squamous cell carcinoma (HNSCC) is a significant global health challenge. The identification of reliable prognostic biomarkers and construction of an ac-curate prognostic model are crucial. Methods In this study, mRNNA expression data and clinical data of HNSCC patients from The Cancer Genome Atlas (TCGA) were used. Overlapping candidate genes (OCGs) were identified by intersecting differentially expressed genes (DEGs)and prognosis-related genes. Best prognostic genes were selected using LASSO-COX regression based on OCGs, and a risk score was developed using the Cox coefficient of each gene. The prognostic power of the risk score was assessed using Kaplan-Meier survival analysis and time-dependent ROC analysis. Univariate and multivariate Cox regression were performed to identify independent prognostic parameters, which were used to construct a nomogram. The predictive accuracy of the nomogram was evaluated using calibration plots. Functional enrichment analysis of risk score related genes was performed to explore the potential biological pathways. External validation was conducted using data from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Results FADS3, TNFRSF12A, TJP3, and FUT6 were screened to be significantly related to prognosis in HNSCC patients. The risk score effectively stratified patients into high-risk group with poor overall survival (OS) and low-risk group with better OS. Risk score, age, clinical M stage, clinical N stage were regarded as independent prognostic parameters by Cox regression analysis and used to construct a nomogram. The nomogram performed well in 1-, 2-, 3-, 5- and 10-year survival predictions. Functional enrichment analysis suggested that tight junction was closely related to the cancer. In addition, the prognostic power of the risk score was validated by external data sets. Conclusions This study constructed a gene-based model integrating clinical prognostic parameters to accurately predict prognosis in HNSCC patients.

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Section: Discussionsupporting

confidence: 92%

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma

Li,

Liu

et al. 2023

Preprint

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“…FUT6 belongs to the fucosyltransferas family and is responsible for fucosylation synthesis. A recent study revealed that FUT6 suppresses the proliferation, migration, invasion, and EGF-induced epithelial-mesenchymal transition in HNSCC cells [ 37 ], which corroborated our findings. In addition, in another signature based on metabolic enzymes, FUT6 was also identified as a protective biomarker [ 10 ].…”

Section: Discussionsupporting

confidence: 91%

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma

Li,

Liu

et al. 2024

Heliyon

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“…Therefore, SCAND1-MZF1-based gene repression of CTNNB1 can minimize EMT-TF gene expression and thus reverse EMT. Our experiments also indicated that SCAND1-MZF1 can minimize the tumor microenvironmental EMTinducing mitogenic factors, such as EGF, FGF, extracellular HSP90, and exosomes involved in activating EMT [10,56,57]. Therefore, SCAND1-MZF1-based gene repression of MAP3Ks and MAPKs can reduce mitogenic and EMT-inducing signals from EGFR and FGFR.…”

Section: Discussionsupporting

confidence: 55%

SCAND1 Reverts EMT and Suppresses Tumor Growth and Collective Migration

Eguchi¹,

Csizmadia²,

Prince³

et al. 2022

Preprint

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Epithelial-mesenchymal transition (EMT) is a reversible cellular program that transiently places epithelial (E) cells into pseudo-mesenchymal (M) cell states. The malignant progression and resistance of many types of carcinomas depends on EMT activation, partial EMT and hybrid E/M status in neoplastic cells. EMT is activated by tumor microenvironmental TGFβ signal and EMT-inducing transcription factors, such as ZEB1/2 in tumor cells. However, reverse EMT factors are less studied. We demonstrate that transcription factor SCAND1 can revert mesenchymal and hybrid E/M phenotype of cancer cells to a more epithelial, less invasive status and inhibit their proliferation and migration. SCAND1 is a SCAN domain-containing protein and hetero-oligomerizes with SCAN-zinc finger transcription factors, such as MZF1, for accessing DNA and transcriptional co-repression of target genes. We found that SCAND1-MZF1 co-expression and interaction correlated with maintaining epithelial features, whereas the simultaneous loss of SCAND1 and MZF1 correlated with mesenchymal features of tumor cells. Overexpression of SCAND1 over endogenous MZF1 in DU-145 prostate cancer cells reverted their hybrid E/M status into cobblestone morphology with increased epithelial adhesion by E-cadherin and β-catenin relocation. Consistently, co-expression analysis in TCGA PanCancer Atlas revealed that both SCAND1 and MZF1 co-express and are negatively correlated with EMT driver genes, including CTNNB1, ZEB1, ZEB2 and TGFBR, in prostate tumor specimens. In addition, SCAND1 overexpression suppressed tumor cell proliferation by reducing the MAP3K-MEK-ERK signaling pathway. Of note, SCAND1-overexpressing DU-145 cells migrated slower than control cells with decreased lymph node metastasis of prostate cancer in a mouse tumor xenograft model. Kaplan-Meyer analysis showed high expression of MZF1 and SCAND1 to correlate with better prognoses in pancreatic cancer and head and neck cancers, although with poorer prognosis in kidney cancer. Overall, these data suggest that the combination of SCAND1-MZF1 complexes may revert the EMT mechanism in cancer to establish an epithelial phenotype. These effects seem to include co-repression of EMT-driver genes and suppression of tumor cell proliferation via inhibition of the MAP3K-MEK-ERK signaling pathway.

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FUT6 inhibits the proliferation, migration, invasion, and EGF-induced EMT of head and neck squamous cell carcinoma (HNSCC) by regulating EGFR/ERK/STAT signaling pathway

Cited by 11 publications

References 55 publications

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma

SCAND1 Reverts EMT and Suppresses Tumor Growth and Collective Migration

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