Short Telomeres Limit Tumor Progression  In Vivo by Inducing Senescence

Feldser, D. and Greider C. W. 2007. Cancer Cell 11, 461-469

Speaker: Yute Chang (張有德)             Time: 14:00-15:00; Oct 3, 2007

Commentator: Dr. Yao Chang (張堯老師)    Place: Room 601

Abstract:

        Cellular senescence, a term used to describe the state of irreversible growth arrest, was defined by Hayflick and Moorhead in 1961. The mechanisms and physiological roles of cellular senescence are still controversial and largely unknown. In general the causes of cellular senescence could be telomeres shortening, activating oncogene, stress and/or DNA damage. A telomere consists of hundreds of tandemly repeated sequence and lies at the end of chromosome. Because of end-replication problem (primer region can not be replicated) telomeres become shorter and shorter and eventually lose their protective ability to prevent chromosome damage. Dysfunctional telomeres are reported to trigger a DNA damage response and enable the cells to undergo cell cycle arresting. In some case the arrest is permanent and irreversible, named telomere-dependent senescence¹. Short telomeres can induce apoptosis and senescence in cancer cell in vitro². Short telomeres can also decrease tumor formation in vivo through increased DNA damage and apoptosis but the involvement of senescence-related pathway has rarely reported. In this article the authors demonstrated the tumor-suppressive effect of short telomere-induced senescence in Burkitt’s lymphoma mouse model. More importantly, the suppression is p53-dependent and still effective even when apoptosis is blocked. Thus in the absence of apoptosis, telomere-mediated senescence effectively limit lymphoma growth in vivo. This result gives us a hint that

telomerase can be a therapeutic target in cancer treatment.

References:

1. Campisi, J. and d’adda di Fagagna, F. 2007. Cellular Senescence: When bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8. 729-740.

2. Collado, M., Blasco, M. A., and Serrano, M. 2007. Cellular Senescence in Cancer and Aging. Cell. 130. 223-233.