کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2107875 1083708 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evidence that Mitotic Exit Is a Better Cancer Therapeutic Target Than Spindle Assembly
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Evidence that Mitotic Exit Is a Better Cancer Therapeutic Target Than Spindle Assembly
چکیده انگلیسی

SummaryCurrent antimitotics work by perturbing spindle assembly, which activates the spindle assembly checkpoint, causes mitotic arrest, and triggers apoptosis. Cancer cells can resist such killing by premature exit, before cells initiate apoptosis, due to a weak checkpoint or rapid slippage. We reasoned blocking mitotic exit downstream of the checkpoint might circumvent this resistance. Using single-cell approaches, we showed that blocking mitotic exit by Cdc20 knockdown slowed cyclin B1 proteolysis, thus allowed more time for death initiation. Killing by Cdc20 knockdown did not require checkpoint activity and can occur by intrinsic apoptosis or an alternative death pathway when Bcl2 was overexpressed. We conclude targeting Cdc20, or otherwise blocking mitotic exit, may be a better cancer therapeutic strategy than perturbing spindle assembly.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 16, Issue 4, 6 October 2009, Pages 347–358
نویسندگان
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