| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 10870440 | FEBS Letters | 2015 | 9 Pages |
Abstract
Clinical applications of a chemotherapeutic agent, 5-fluorouracil (5-FU) in oral squamous cell carcinoma (OSCC) have been limited because of drug resistance. This study aimed to identify novel mechanisms of 5-FU resistance. Here we found increased osteopontin (OPN) gene expression in OSCC tissues with resistance to 5-FU-based chemoradiotherapy. OPN overexpression in OSCC cells led to 5-FU resistance and abrogated the prosurvival effect of the drug in a mouse xenograft model. OPN-induced 5-FU resistance required integrin αvβ3. Targeting integrin αvβ3 reversed the resistance in a 5-FU-resistant clone highly expressing OPN. Our data suggest that the OPN-integrin αvβ3 axis is crucial for 5-FU resistance in OSCC.
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Authors
Takuya Nakamura, Satoru Shinriki, Hirofumi Jono, Mitsuharu Ueda, Masashi Nagata, Jianying Guo, Mitsuhiro Hayashi, Ryoji Yoshida, Tomoko Ota, Kazutoshi Ota, Kenta Kawahara, Yoshihiro Nakagawa, Satoshi Yamashita, Hideki Nakayama, Akimitsu Hiraki,