Nuclear signalling by tumour-associated antigen EpCAM (Nat Cell Biol, 2009, doi:10.1038/ncb1824)

報告日期: 2009/04/24
報告時間: 15:10/16:00
報告學生: 謝宜珊
講評老師: 王育民
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980424-1.pdf

Nuclear signalling by tumour-associated antigen EpCAM

Nat Cell Biol. 2009 Feb;11(2):162-71. Epub 2009 Jan 11.

 

 

Student: 謝宜珊

Commentator: 王育民老師

Time: 15:10-16:00, Apr 24, 2009

Place: Room 602

 

Abstract:

EpCAM (epithelial cell adhesion molecule) is a cell surface molecule that is known to be highly expressed in colon and other epithelial carcinomas. The role of EpCAM in proliferation, and its association with cancer is poorly explained by proposed cell adhesion functions. In this study, the authors show here that at EpCAM is activated as a mitogenic signal transducer through self aggregation. This causes shedding of its ectodomain EpEX and nuclear translocation of its short intracellular domain, EpIC. Inducible cleavage of EpCAM is sequentially catalyzed by the transmembrane proteases TACE and presenilin-2. Pharmacological inhibition of either protease impairs the growth-promoting signalling by EpCAM. Cytoplasmically released EpIC associates with components of the Wnt pathway to form a ternary complex including the adaptor proteins FHL2 and b-catenin, and the transcription factor Lef-1. After nuclear translocation, this complex is binding to Lef consensus sites on DNA, induces c-myc, and initiates cell proliferation. This findings may set new paths for development of therapeutic interventions in cancer that prevent EpCAM signaling.

 

 

Reference :

Medina, M. & Dotti, C. G. RIPped out by presenilin-dependent gamma-secretase. Cell

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