Title:
Cellular senescence in aging, disease, and cancer

 

Speaker:
Akira Shimamoto
Department of Cellular and Molecular Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University

 

Abstract:
Cellular senescence is a tumor suppressor mechanism triggered by intrinsic and extrinsic stressors including telomere dysfunction, aberrant oncogenic signaling, and DNA damage responses. These stress signals induce a variety of outcomes including permanent cell growth arrest, morphological changes, changes in gene expression profiles, and senescence-associated secretory phenotype (SASP) which causes chronic inflammation involving clearance of senescent cells (1). In addition, senescence also contributes to functional declines of organs and tissues associated with aging, and senescence program is regulated by typical tumor suppressor genes such as p53-p21 and p16-Rb (1). Dysregulation of the program is associated with diseases including premature aging (2) and cancer (1). Recent progress in this field identified another senescence mechanism, that is senescence-associated miRNAs (SA-miRs), which could induce cellular senescence and be applicable to cancer therapy.
In this seminar, I’d like to present our recent research efforts including microRNA-based regulation of senescence (3), reprogramming of cells with premature aging syndrome caused by telomere dysfunction (4), and finally, cancer dormancy formation induced by cellular senescence mechanism using a cancer stem cell model.

 

References:
1.Kuilman T1, Michaloglou C, Mooi WJ, Peeper DS. Genes Dev. 24:2463-2479. 2010
2.Shimamoto A, Sugimoto M, Furuichi Y. Int J Clin Oncol. 9:288-298. 2004
3.Xu D, Takeshita F, Hino Y, Fukunaga S, Kudo Y, Tamaki A, Matsunaga J, Takahashi RU, Takata T, Shimamoto A, Ochiya T, Tahara H. J Cell Biol. 193:409-424. 2011
4.Shimamoto A, Kagawa H, Zensho K, Sera Y, Kazuki Y, Osaki M, Oshimura M, Ishigaki Y, Hamasaki K, Kodama Y, Yuasa S, Fukuda K, Hirashima K, Seimiya H, Koyama H, Shimizu T, Takemoto M, Yokote K, Goto M, Tahara H. PLoS One. 9(11):e112900. 2014.