Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL (Nat Med, 2007, 13:1070-1077)

報告日期: 2007/11/23
報告時間: 15:10/16:00
報告學生: 黃彥彰
講評老師: 張權發
附件下載:

http://basicmed.med.ncku.edu.tw/upload_data/961123-1.pdf

Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL

NATURE MEDICINE 2007 SEPTEMBER Vol.13 1070-1077

 

Speaker: 黃彥彰                        

Commentator: 張權發 老師              

Date: 2007/11/23

Time: 15:10~16:00

Location: Room 602

Abstract

Apoptosis plays a central role both in development and in homeostasis of metazoans. Deregulation of apoptosis can disrupt the delicate balance between cell proliferation and cell death and can lead to diseases such as cancer. A new therapeutic strategy is activating apoptosis pathway in tumor cells. Apo2L/TRAIL stimulates cancer cell death through the proapoptotic receptors DR4 and DR5, but the determinants of tumor susceptibility to this ligand are not fully defined. In this paper, mRNA expression of the peptidyl O-glycosyltransferase GALNT14 correlated with Apo2L/TRAIL sensitivity in many cancer cells. RNA interference of GALNT14 reduced the O-glycosylaion of death receptors and cellular Apo2L/TRAIL sensitivity. Whereas overexpression of GALNT14 increased responsiveness. O-glycosylation of DR4 and DR5 in cancer cells modulates sensitivity to Apo2L/TRAIL by promoting ligand-induced receptor clustering and consequent caspase-8 activation. These findings provide new insight into the potential utility of specific O-glycosylation enzymes or their modified targets as predictive biomarkers for Apo2L/TRAILbased cancer therapy.