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Gelsolin regulates cisplatin sensitivity in human head‐and‐neck cancer
Author(s) -
Wang PeiWen,
Abedini Mohammad R.,
Yang LiXing,
Ding AnnAnn,
Figeys Daniel,
Chang JangYang,
Tsang Benjamin K.,
Shieh DarBin
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28928
Subject(s) - xiap , cisplatin , gelsolin , cancer research , apoptosis , downregulation and upregulation , inhibitor of apoptosis , cancer cell , cancer , gene silencing , head and neck cancer , biology , chemotherapy , medicine , caspase , programmed cell death , microbiology and biotechnology , actin , biochemistry , gene
Chemoresistance is a major challenge in cancer therapy. Cisplatin is commonly used for chemotherapy in patients with head‐and‐neck cancer (HNC), but it increases control of the disease by only 10–15%. Downregulation of proapoptotic pathways is a key determinant for chemoresistance in which gelsolin (GSN) is critically involved. We analyzed the association between GSN expression and cisplatin resistance in HNC cell lines, animals with HNC and cancer tissue samples from 58 cisplatin‐treated patients with HNC. GSN expression levels were positively associated with chemoresistance in vitro and in vivo . Cisplatin‐induced GSN downregulation was associated with the cleavage of GSN and the promotion of apoptosis. GSN silencing facilitated cisplatin‐induced apoptosis in chemoresistant cells. In contrast, intact gelsolin was prosurvival in the presence of cisplatin by interacting with X‐linked inhibitor of apoptosis protein (XIAP). In chemosensitive cells, cisplatin suppressed GSN–XIAP interaction, promoted translocation of XIAP from the perinuclear region to the nucleus and induced apoptosis. In chemoresistant cells, GSN was highly expressed, and cisplatin had no significant effect on GSN–XIAP interaction and apoptosis. We conclude that GSN is important for chemoresistance in HNC and may be an appropriate therapeutic target in chemoresistant cancers.