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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

Cancer Gene Therapy volume 30, pages 182–191 (2023)Cite this article

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Abstract

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.

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Fig. 1: FUT6 was down-regulated in HNSCC tissues.
Fig. 2: The effects of FUT6 on cell proliferation in HNSCC cells.
Fig. 3: The effects of FUT6 on cell migration and invasion in HNSCC cells.
Fig. 4: In vivo tumor xenograft study.
Fig. 5: The effects of FUT6 on the EGFR signaling pathway and EMT in Cal-27, FaDU, and HSC-3 cells.
Fig. 6: FUT6 control EMT through EGF-induced EGFR/ERK/STAT signaling in Cal-27 and FaDU cells.

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Data available on request from the authors.

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Acknowledgements

This study was supported by the Outstanding Young Talent Project of Zunyi Medical University (17zy-002), the Sixth Talent Foundation in Guizhou province (rcjd2019-9), and the National Natural Science Foundation of China (NSFC, 82160112).

Funding

This study was supported by the Outstanding Young Talent Project of Zunyi Medical University (17zy-002), the Sixth Talent Foundation in Guizhou province (rcjd2019-9), the Science and Technology Plan Project of Guizhou Province (QIAN KE HE JI CHU-ZK(2021)YI BAN 451), and the National Natural Science Foundation of China (82160112).

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  1. These authors contributed equally: Qian Wang, Chengcheng Liao.

Authors and Affiliations

  1. Oral Disease Research Key Laboratory of Guizhou Tertiary Institution, School of Stomatology, Zunyi Medical University, 563000, Zunyi, Guizhou Province, China

    Qian Wang, Chengcheng Liao & Jianguo Liu

  2. Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University, 563000, Zunyi, Guizhou Province, China

    Chengcheng Liao, Zhangxue Tan, Xiaoyan Guan, Hao Li & Zhongjia Tian

  3. Microbial Resources and Drug Development Key Laboratory of Guizhou Tertiary Institution, Life Sciences Institute, Zunyi Medical University, 563000, Zunyi, China

    Xiaolan Li

  4. Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 563000, Zunyi, Guizhou Province, China

    Jiaxing An

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Contributions

JA and JL conceived and supervised the research. JA and QW provide the research foundation. CL and ZT complete the main cell and animal experiment. HL, ZT, and KY participated in the initial phase of experiments. XG participate in data analysis and figure preparation. XL review and edit the manuscript. QW and CL wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jianguo Liu or Jiaxing An.

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Wang, Q., Liao, C., Tan, Z. et al. 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. Cancer Gene Ther 30, 182–191 (2023). https://doi.org/10.1038/s41417-022-00530-w

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