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Osteopontin‐integrin α v β 3 axis is crucial for 5‐fluorouracil resistance in oral squamous cell carcinoma
Author(s) -
Nakamura Takuya,
Shinriki Satoru,
Jono Hirofumi,
Ueda Mitsuharu,
Nagata Masashi,
Guo Jianying,
Hayashi Mitsuhiro,
Yoshida Ryoji,
Ota Tomoko,
Ota Kazutoshi,
Kawahara Kenta,
Nakagawa Yoshihiro,
Yamashita Satoshi,
Nakayama Hideki,
Hiraki Akimitsu,
Shinohara Masanori,
Ando Yukio
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.12.004
Subject(s) - osteopontin , fluorouracil , integrin , basal cell , cancer research , medicine , oncology , pathology , chemistry , cancer , receptor
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 α v β 3 . Targeting integrin α v β 3 reversed the resistance in a 5‐FU‐resistant clone highly expressing OPN. Our data suggest that the OPN‐integrin α v β 3 axis is crucial for 5‐FU resistance in OSCC.