title: Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis.
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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Iwate Medical University, Morioka, Japan.|Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Shiga
authors.affiliation: Division of Cancer Glycosylation Research, Tohoku Pharmaceutical University, Sendai, Japan.|Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Miyagi Cancer Center, Natori, Japan.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Sato
authors.affiliation: Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Division of Cancer Glycosylation Research, Tohoku Pharmaceutical University, Sendai, Japan.
authors.forename: Setsuko
authors.initials: S
authors.lastname: Moriya
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hosono
authors.affiliation: Division of Cancer Glycosylation Research, Tohoku Pharmaceutical University, Sendai, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Miyagi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002855:Chromatography, Thin Layer; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000032:analysis / Q000096:biosynthesis*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C465436:Neu3 protein, human; D009439:Neuraminidase
keywords: Epidermal growth factor receptor; MMP9; head and neck squamous cell carcinoma; lymph node metastasis; sialidase