がん研セミナー（１１月２８日）のお知らせ

演題：Mechanisms of chromosomal instability in human cancers

演者：Duane Compton 博士（Geisel School of Medicine at Dartmouth, Hanover NH, USA）

日時：2014年 11月28日（金）14:00-14:45

場所：吉田講堂

連絡先：広田　亨（内線5251）

抄録：　

Most solid tumors are aneuploid and many have defects in chromosome segregation causing them to frequently mis-segregate whole chromosomes in a phenomenon called chromosomal instability (CIN). Previously, we used live cell imaging and clonal cell analyses to evaluate chromosome segregation in chromosomally stable and unstable human cells. These experiments revealed that the most common mitotic defect in tumor cells with CIN is the persistence of erroneous attachment of spindle microtubules to kinetochores on chromosomes (i.e. merotely). In normal diploid cells erroneous attachments arise spontaneously but are efficiently corrected by high dynamic turnover of kinetochore-microtubule attachments to preserve genome stability. However, kinetochore microtubule attachments in cancer cells with CIN are inherently more stable that those in normal diploid cells preventing efficient error correction. The observed differences in attachment stability account for the persistence of mal-attachments into anaphase, where they cause chromosome mis-segregation. Importantly, strategically decreasing the stability of kinetochore- microtubule attachments suppresses CIN and restores faithful chromosome segregation fidelity to aneuploid cancer cells.

These experiments unveil a homeostatic control mechanism for regulating kinetochore microtubule attachments during mitosis. Moreover, we have developed cell permeable small molecules that specifically suppress chromosome mis-segregation in CIN tumor cells without affecting diploid cells and we have discovered that tumor cells rapidly acquire adaptive resistance to targeted therapy.

＊外部の研究者のご来聴を歓迎いたします。尚、本セミナーの内容は専門的であり、医学・生物分野の研究に携わる方を対象としております。