FBLIM1 enhances oral cancer malignancy via modulation of the epidermal growth factor receptor pathway

• Published in: Molecular carcinogenesis Vol. 57; no. 12; pp. 1690 - 1697
• Main Authors: Toeda, Yuriko, Kasamatsu, Atsushi, Koike, Kazuyuki, Endo‐Sakamoto, Yosuke, Fushimi, Kazuaki, Kasama, Hiroki, Yamano, Yukio, Shiiba, Masashi, Tanzawa, Hideki, Uzawa, Katsuhiro
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2018
• Subjects: Carcinogenesis; Cell proliferation; Clopidogrel; Epidermal growth factor; epidermal growth factor receptor; Epidermal growth factor receptors; filamin‐binding LIM protein 1; Immunohistochemistry; Inflammation; Invasiveness; LIM protein; Malignancy; Oral cancer; Oral squamous cell carcinoma; Osteomyelitis; Polymerase chain reaction; RNA-directed DNA polymerase; siRNA; Squamous cell carcinoma; Therapeutic applications; clopidogrel; oral squamous cell carcinoma; epidermal growth factor receptor; filamin-binding LIM protein 1
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.22889

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.