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Title 

TWEAK/Fn14 signaling mediates gastric cancer cell resistance to 5-fluorouracil via NF-kB activation

Authors 

Oh Hyung KwonJong Hwan KimSeon-Young KimYong Sung Kim

Publisher 

Spandidos Publications

Issue Date 

2014

Citation 

International Journal of Oncology, vol. 44, no. 2, pp. 583-590

Abstract 

Chemoresistance is one of the most serious problems in the treatment of cancer. In the present study, we show that Fn14 promotes resistance to 5-fluorouracil (5-FU) in gastric cancer (GC). We found that 5-FU treatment upregulated Fn14 expression in various cancer cell lines, including GC cell lines, and that knockdown of Fn14 using shRNA accelerated 5-FU sensitivity. In contrast, Fn14 overexpression or TWEAK treatment promoted resistance to 5-FU. Furthermore, we investigated the mechanisms underlying Fn14-mediated chemoresistance. We first revealed that 5-FU-mediated upregulation of Fn14 occurred as a result of NF-κB activation, indicating that 5-FU-mediated NF-κB activation was the principal event underlying Fn14 upregulation and 5-FU resistance in GC. Taken together, our results suggest that Fn14 is a novel therapeutic target and that inhibition of Fn14 combined with 5-FU treatment may be an effective molecular therapeutic strategy to treat 5-FU-resistant gastric cancers

ISSN 

1019-6439

Link 

http://dx.doi.org/10.3892/ijo.2013.2211

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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