RRC ID 54068
Author Toeda Y, Kasamatsu A, Koike K, Endo-Sakamoto Y, Fushimi K, Kasama H, Yamano Y, Shiiba M, Tanzawa H, Uzawa K.
Title FBLIM1 enhances oral cancer malignancy via modulation of the epidermal growth factor receptor pathway.
Journal Mol Carcinog
Abstract Filamin-binding LIM protein 1 (FBLIM1) is related to regulation of inflammatory responses, such as chronic recurrent multifocal osteomyelitis; however, the relevance of FBLIM1 in oral squamous cell carcinoma (OSCC) is unknown. The aim of the current study was to elucidate the possible role of FBLIM1 in the carcinogenesis of OSCC. We analyzed FBLIM1 expression using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), immunoblot analysis, and immunohistochemistry. The expression levels of FBLIM1 were up-regulated significantly (P < 0.05) in OSCC-derived cell lines and primary OSCCs specimens compared with normal counterparts. FBLIM1 expression also was correlated with the primary tumoral size (P < 0.05) and vascular invasion (P < 0.05). We then assessed tumoral progression after treatment with FBLIM1 siRNA and clopidogrel, an antiplatelet agent. Similar to the FBLIM1 knockdown effect, clopidogrel-treated cells had attenuated functions of proliferation, migration, and invasiveness. Interestingly, clopidogrel treatment led to down-regulation of epidermal growth factor receptor (EGFR) and FBLIM1. These findings identify FBLIM1 as a putative therapeutic target by using clopidogrel for inhibiting over activation of EGFR signaling to prevent OSCC malignancy.
Volume 57(12)
Pages 1690-1697
Published 2018-12-1
DOI 10.1002/mc.22889
PMID 30129678
MeSH Aged Aged, 80 and over Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Adhesion Molecules / genetics* Cell Adhesion Molecules / metabolism* Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Clopidogrel / pharmacology* Cytoskeletal Proteins / genetics* Cytoskeletal Proteins / metabolism* ErbB Receptors / metabolism Female Gene Expression Regulation, Neoplastic Humans Male Middle Aged Mouth Neoplasms / genetics Mouth Neoplasms / metabolism Mouth Neoplasms / pathology* Neoplasm Staging Signal Transduction / drug effects* Tumor Burden Up-Regulation
IF 3.825
Times Cited 5
Human and Animal Cells HO-1-u-1(RCB2102)