Aberrant myosin 1b expression promotes cell migration and lymph node metastasis of HNSCC

Gaku Ohmura, Takahiro Tsujikawa, Tomonori Yaguchi, Naoshi Kawamura, Shuji Mikami, Juri Sugiyama, Kenta Nakamura, Asuka Kobayashi, Takashi Iwata, Hiroshi Nakano, Taketoshi Shimada, Yasuo Hisa, Yutaka Kawakami

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 nodemetastases in a cervical lymph node metastatic mouse model system. Implications: 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. Mol Cancer Res; 13(4); 721-31.

Original languageEnglish
Pages (from-to)721-731
Number of pages11
JournalMolecular Cancer Research
Volume13
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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