RESUMEN
Glycosylation change is one of the landmark events of tumor occurrence and development, and tumor cells may be inhibited by regulating the aberrant expression of glycosyltransferases. Currently, fucosyltransferase VI (FUT6), which is involved in the synthesis of α-1, 3 fucosyl bond, has been detected to be closely associated with multiple tumors, but its function and mechanism in head and neck squamous cell carcinoma (HNSCC) still need further research. In this study, FUT6 knockdown and overexpression strategies were used to investigate the effects of FUT6 on cell proliferation, migration, and invasion, as well as the growth and metastasis of HNSCC in a xenografts mouse model. The protein expression levels of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), Signal Transducer and Activator of Transcription (STAT), protein kinase B (AKT), c-Myc, and epithelial-mesenchymal transition (EMT) markers were determined by western blot analysis. Our research found that the mRNA expression of FUT6 was lower in HNSCC tissues than in normal mucosal epithelial tissues. In Cal-27 and FaDu cells, FUT6 overexpression inhibited cell proliferation, migration and invasion, causing upregulation of ZO-1 and E-cadherin, downregulation of N-cadherin and Vimentin, and finally decreased the phosphorylation levels of EGFR, ERK, STAT, and c-Myc. In HSC-3 cells, knockdown of FUT6 promoted cell proliferation, migration and invasion, downregulating ZO-1 and E-cadherin, upregulating N-cadherin and Vimentin, and increased the phosphorylation levels of EGFR, ERK, STAT, and c-Myc. In the HNSCC xenografts mouse, FUT6 overexpression inhibited tumor growth and metastasis. In summary, FUT6 controls the proliferation, migration, invasion, and EGF-induced EMT of HNSCC by regulating EGFR/ERK/STAT signaling pathway, indicating its potential future therapeutic application for HNSCC.
Asunto(s)
Factor de Crecimiento Epidérmico , Neoplasias de Cabeza y Cuello , Humanos , Animales , Ratones , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/farmacología , Vimentina , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Transducción de Señal , Receptores ErbB/metabolismo , Proliferación Celular , Cadherinas/metabolismo , Neoplasias de Cabeza y Cuello/genética , Movimiento Celular/genética , Fucosiltransferasas/genética , Fucosiltransferasas/metabolismoRESUMEN
Glycosylation changes are key molecular events in tumorigenesis, progression and glycosyltransferases play a vital role in the this process. FUT8 belongs to the fucosyltransferase family and is the key enzyme involved in N-glycan core fucosylation. FUT8 and/or core fucosylated proteins are frequently upregulated in liver, lung, colorectal, pancreas, prostate,breast, oral cavity, oesophagus, and thyroid tumours, diffuse large B-cell lymphoma, ependymoma, medulloblastoma and glioblastoma multiforme and downregulated in gastric cancer. They can be used as markers of cancer diagnosis, occurrence, progression and prognosis. Core fucosylated EGFR, TGFBR, E-cadherin, PD1/PD-L1 and α3ß1 integrin are potential targets for tumour therapy. In addition, IGg1 antibody defucosylation can improve antibody affinity, which is another aspect of FUT8 that could be applied to tumour therapy.
RESUMEN
Glycosylation is an important posttranslational modification of proteins, and it has a profound influence on diverse life processes. An abnormal polysaccharide structure and mutation of the glycosylation pathway are closely correlated with human cancer progression. Glycoproteins such as EGFR, E-cadherin, CD44, PD-1/PD-L1, B7-H3 and Muc1 play important roles in the progression of head and neck squamous cell carcinoma (HNSCC), and their levels of glycosylation and changes in glycosyl structure are closely linked to HNSCC progression and malignant transformation. The regulation of protein glycosylation in HNSCC provides potential strategies to control cancer stem cell (CSC) subgroup expansion, epithelial-mesenchymal transition (EMT), tumor-related immunity escape and autophagy. Glycoproteins with altered glycosylation can be used as biomarkers for the early diagnosis, monitoring and prognostication of HNSCC. However, the glycobiology of cancer is still a new field that needs to be deeply studied, especially in HNSCC.