کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10901350 1084694 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nuclear accumulation of Yes-Associated Protein (YAP) maintains the survival of doxorubicin-induced senescent cells by promoting survivin expression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Nuclear accumulation of Yes-Associated Protein (YAP) maintains the survival of doxorubicin-induced senescent cells by promoting survivin expression
چکیده انگلیسی
Although chemotherapeutic drugs can induce senescence to prohibit further division of tumor cells, senescence could also promote tumorigenesis mainly through a senescence-associated secretory phenotype. Therefore, senescent tumor cells should be eliminated immediately to prevent drug resistance and recurrence. Here, we used a doxorubicin-induced senescence model to explore the mechanism underlying the survival of therapy-induced senescent cells. After low-dose doxorubicin treatment, tumor cells turned on a senescence program and became large and flattened, increasing their contact area with the extracellular matrix (ECM). Furthermore, Yes-associated protein (YAP) accumulated in the nucleus and YAP activity was increased in doxorubicin-induced senescent cells. Knockdown of YAP increased the sensitivity of cells to low-dose doxorubicin treatment, causing apoptosis rather than senescence. Moreover, the anti-apoptotic gene survivin, a YAP target gene, was overexpressed in senescent cells. Inhibition of survivin could lead to selective elimination of senescent cells through apoptosis. Our study indicates that nuclear accumulation of YAP could promote the survival of senescent cells by increasing survivin expression. Therefore, targeting YAP or survivin might be a new strategy for clearing senescent cancer cells during drug treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 375, Issue 1, 28 May 2016, Pages 84-91
نویسندگان
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