Basic Medicine, Oncology, Molecular and Cellular Biology
How Chromosomal Instability Arises and How It is Involved in Oncogenesis and Cancer Progression: Detailed Analysis of Chromosome Motion
Medical Sciences Course
- Master / Doctoral Degree
- TANAKA, Kozo
Professor, M.D. Ph.D.
kozo.tanaka.d2*tohoku.ac.jp (Please convert "*" into "@".)
- Mechanism of chromosomal instability in cancer
- Mechanism of oncogenic transformation through chromosomal instability
- Cancer therapy targeting mitosis
chromosomal instability, oncogenesis, chromosome segregation, mitosis, cancer therapy
live cell imaging, cell culture, immunofluorescence staining, protein analysis, genetically modified mouse
Cancer is characterized by unrestricted proliferation of cells. Our body is made up with sixty trillion cells as a result of proliferation (division) of one fertilized egg. In each cell of our body, 46 chromosomes are properly transmitted. On the other hand, most of the cancer cells show abnormalities in chromosome number and structure due to chromosomal instability, a condition in which chromosome missegregation occurs at a high rate. Chromosomal instability is not just a result of oncogenic transformation, but supposed to be closely related to oncogenesis, although its detailed mechanism is elusive. Chromosome segregation is a very dynamic process, and has been attracted scientists for over hundred years. We try to build up and verify hypotheses through our observation of chromosome motion, avoiding preconceptions. We have discovered a molecule involved in chromosome segregation, CAMP, and revealed that Nup188, a component of the nuclear pore complex, plays a role in chromosome segregation. Through these researches, using culture cells and mice, we are aiming to clarify how chromosomal instability is related to oncogenesis. We are also trying to develop novel strategies to cure cancer by targeting its characteristics like chromosomal instability.
Figure 1. Process of chromosome segregation
Figure 2. Chromosome misalignment in CAMP-depleted cells
- Iemura K, Tanaka K. Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules. Nat Commun. 6:6447, 2015.
- Amin MA, et al. CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment. J Cell Sci. 127(13):2818-2824, 2014.
- Itoh G, et al. CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment. EMBO J. 30(1):130-144, 2011.
- Kawashima S, et al. Global analysis of core histones reveals nucleosomal surfaces required for chromosome bi-orientation. EMBO J. 30(16):3353-3367, 2011.
- Kitamura E, et al. Kinetochores generate microtubules with distal plus ends: their roles and limited lifetime in mitosis. Dev Cell 18(2):248-259, 2010.