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

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Title
TWEAK/Fn14 signaling mediates gastric cancer cell resistance to 5-fluorouracil via NF-kB activation
Author(s)
Oh Hyung Kwon; Jong Hwan KimSeon-Young Kim; Yong Sung Kim
Bibliographic Citation
International Journal of Oncology, vol. 44, no. 2, pp. 583-590
Publication Year
2014
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
Keyword
chemoresistance5-FUgastric cancerNF-κBFn14
ISSN
1019-6439
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/ijo.2013.2211
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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