Chemokine signaling via the CXCR2 receptor reinforces senescence (Cell, 2008, 133:1006-1018)

報告日期: 2008/10/21
報告時間: 16:00/16:50
報告學生: 賴曉菁
講評老師: 黃溫雅
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971021-2.pdf

Chemokine signaling via the CXCR2 receptor reinforces senescence

Cell (2008) 133: 1006-1018

 

Speaker: 賴曉菁

Commentator : 黃溫雅 老師

Time: 16:00-16:50, 2008/10/21

Place: Room 602

 

Abstract:

    Cellular senescence can be induced by various stimuli, such as DNA damage and oncogene activation, resulting in cells that lose their ability to divide but remain metabolically active. Since senescence has been considered as an obstacle toward tumorigenesis, it is important to understand how senescence is regulated and how tumor cells bypass it. This study found that knockdown of CXCR2 recovered cell growth from senescence, and CXCR2 overexpression led to premature senescence in a p53-dependent manner. During senescence, expression of CXCR2 was increased, and ligands of CXCR2, such as interleukin (IL)-8 and growth related oncogene (GRO)-a, were also upregulated. The upregulation of CXCR2 ligands involved activation of nuclear factor (NF)-kB and C/EBP. Besides the increased expression of CXCR2 and its ligands, activation of CXCR2 through binding to its ligands was required for cellular senescence. Further examination of tissues in vivo showed that CXCR2 expression was significantly elevated in preneoplastic lesions than in malignant tumors. In addition, a mutated CXCR2 identified from a cancer cell line showed impaired ability to promote senescence. This study suggests that cellular senescence can be reinforced by a positive feedback loop involving CXCR2 and its ligands, and tumor cells may evade senescence through downregulation or inactivation of CXCR2.

 

References

1. Campisi,J. and d’Addadi Fagagna, F. (2007). Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8, 729-740.

2. Narita, M. and Lowe, S. W. (2005). Senescence comes of age. Nat Met 11,920-922.