title: Aberrant Myosin 1b Expression Promotes Cell Migration and Lymph Node Metastasis of HNSCC.
abstract: Lymph node metastasis is the major clinicopathologic feature associated with poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Here, web-based bioinformatics meta-analysis was performed to elucidate the molecular mechanism of lymph node metastasis of human HNSCC. Preferential upregulation of Myosin 1b (MYO1B) transcript in HNSCC datasets was identified. Myo1b mRNA was highly expressed in human HNSCC cells and patient tissue specimens compared with their normal counterparts as shown by quantitative PCR (qPCR) analyses. Immunohistochemistry (IHC)-detected Myo1b expression was significantly correlated with lymph node metastases in patients with oral cancer of the tongue. HNSCC with high expression of Myo1b and chemokine receptor 4 (CCR4), another metastasis-associated molecule, was strongly associated with lymph node metastasis. RNA interference (RNAi) of Myo1b in HNSCC cells, SAS and HSC4, significantly inhibited migratory and invasive abilities through decreased large protrusion formation of cell membranes. Finally, Myo1b knockdown in SAS cells significantly inhibited in vivo cervical lymph node metastases in a cervical lymph node metastatic mouse model system.
  
  
  CONCLUSIONS
  Myo1b is functionally involved in lymph node metastasis of human HNSCC through enhanced cancer cell motility and is an attractive target for new diagnostic and therapeutic strategies for patients with HNSCC.
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto City, Kyoto, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Ohmura
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto City, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsujikawa
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yaguchi
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Kawamura
authors.affiliation: Division of Diagnostic Pathology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Juri
authors.initials: J
authors.lastname: Sugiyama
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto City, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto City, Kyoto, Japan.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto City, Kyoto, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. yutakawa@z5.keio.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003198:Computer Simulation; D030541:Databases, Genetic; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D024461:Myosin Type I / Q000235:genetics* / Q000378:metabolism*; D054398:Receptors, CCR4 / Q000235:genetics / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C515354:CCR4 protein, human; C000594736:MYO1B protein, human; D054398:Receptors, CCR4; D024461:Myosin Type I