RRC ID 67324
Author Ohmura G, Tsujikawa T, Yaguchi T, Kawamura N, Mikami S, Sugiyama J, Nakamura K, Kobayashi A, Iwata T, Nakano H, Shimada T, Hisa Y, Kawakami Y.
Title Aberrant Myosin 1b Expression Promotes Cell Migration and Lymph Node Metastasis of HNSCC.
Journal Mol Cancer Res
Abstract UNLABELLED: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.
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.
Volume 13(4)
Pages 721-31
Published 2015-4-1
DOI 10.1158/1541-7786.MCR-14-0410
PII 1541-7786.MCR-14-0410
PMID 25421751
MeSH Aged Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Cell Movement Cell Proliferation Computer Simulation Databases, Genetic Female Head and Neck Neoplasms / genetics Head and Neck Neoplasms / metabolism Head and Neck Neoplasms / pathology* Humans Lymph Nodes / metabolism Lymph Nodes / pathology* Lymphatic Metastasis Male Myosin Type I / genetics* Myosin Type I / metabolism* Receptors, CCR4 / genetics Receptors, CCR4 / metabolism Squamous Cell Carcinoma of Head and Neck Tongue Neoplasms / genetics Tongue Neoplasms / metabolism Tongue Neoplasms / pathology* Up-Regulation
IF 4.63
Human and Animal Cells SAS(RCB1974) HSC-4(RCB1902)