Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis

Cancer Science

Kiyoto Shiga¹  Kohta Takahashi⁵  Ikuro Sato³  Kengo Kato⁴  Shigeru Saijo⁴  Setsuko Moriya⁵  Masahiro Hosono² 

[1] Department of Otolaryngology–Head and Neck Surgery, Iwate Medical University, Morioka, Japan;Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan;Department of Pathology, Miyagi Cancer Center, Natori, Japan;Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan;Division of Cancer Glycosylation Research, Tohoku Pharmaceutical University, Sendai, Japan

关键词: Epidermal growth factor receptor;    head and neck squamous cell carcinoma;    lymph node metastasis;    MMP9;    sialidase;   

DOI  :  10.1111/cas.12810

来源: Wiley

【 摘 要 】

Abstract

Regional lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) is a crucial event for its progression, associated with a high rate of mortality. Sialidase, a key enzyme for the regulation of cellular sialic acids through catalyzing the initial step of degradation of glycoproteins and glycolipids, has been implicated in cancer progression. To facilitate the development of novel treatments for HNSCC, we have investigated whether sialidase is involved in the progression of this cancer. We found plasma membrane-associated sialidase (NEU3) to be significantly upregulated in tumor compared to non-tumor tissues; particularly, an increase in its mRNA levels was significantly associated with lymph node metastasis. To understand the mechanisms, we analyzed the NEU3-mediated effects on the malignant phenotype using squamous carcinoma HSC-2 and SAS cells. NEU3 promoted cell motility and invasion, accompanied by the increased expression of MMP-9, whereas NEU3 silencing or the activity-null mutant did not. NEU3 enhanced phosphorylation of epidermal growth factor receptor (EGFR), and an EGFR inhibitor, AG1478, abrogated the NEU3-induced MMP9 augmentation. These findings identify NEU3 as a participant in HNSCC progression through the regulation of EGFR signaling and thus as a potential target for inhibiting EGFR-mediated tumor progression.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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