Cancer Science | |
Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis | |
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 】
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.Abstract
【 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.
Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
【 预 览 】
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