Open AccessFOXM 1 mediates resistance to docetaxel in gastric cancer via up‐regulating Stathmin
Author(s) -
Li Xiaoxiao,
Yao Ruyong,
Yue Lu,
Qiu Wensheng,
Qi Weiwei,
Liu Shihai,
Yao Yasai,
Liang Jun
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12216
Subject(s) - stathmin , docetaxel , cancer , cancer research , medicine , biology , pharmacology , biochemistry , phosphorylation
Docetaxel is commonly used as an effective chemotherapeutic drug for gastric cancer patients recently. With the increasing emergence of docetaxel resistance nowadays, identification of suitable biomarkers for predicting chemosensitivity to docetaxel may be a key role for improving therapeutic effects for gastric cancer patients. In this study, we investigated the correlation between the expression of transcription factor forkhead box protein M1 ( FOXM 1) and chemotherapy response to docetaxel in gastric cancer, the possible mechanism for which was further explored. As a result, FOXM 1 overexpression was shown to mediate resistance to docetaxel in gastric cancers. It altered microtubule dynamics to protect tumour cells from docetaxel‐induced apoptosis. Mechanistic investigations revealed that tubulin‐destabilizing protein S tathmin, which mediated docetaxel resistance in FOXM 1‐silenced gastric cancer cells, is a direct down‐stream target of FOXM 1, whereas another microtubule dynamics protein mitotic centromere–associated kinesin (MCAK), shown to be related to docetaxel resistance in gastric cancer cells, is not associated with FOXM 1 expression significantly. These results were further provided by immunohistochemical analysis, indicating that FOXM 1 and S tathmin expression levels were correlated in 103 post‐operational gastric cancer specimens. Moreover, when we attenuated FOXM 1 expression with FOXM 1 inhibitor thiostrepton, docetaxel resistance in gastric cancers was found to be reversed, simultaneously with the down‐regulation of FOXM 1 and S tathmin. Therefore, FOXM 1 can be a useful marker for predicting and monitoring docetaxel response. Through the inhibition of FOXM 1, docetaxel resistance can be reversed, and thus FOXM 1 could be a new therapeutic target in docetaxel‐resistant gastric cancer.