Cell Biology

Journey to the Center of the Cell

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Science  13 Feb 2009:
Vol. 323, Issue 5916, pp. 855
DOI: 10.1126/science.323.5916.855b

The levels of epithelial cell adhesion molecule (EpCAM) are up-regulated in various human carcinomas, suggesting that it may play a role in tumor cell proliferation. EpCAM is a transmembrane glycoprotein found at the plasma membrane and is thought to function primarily in cell adhesion. Maetzel et al. found that EpCAM was subject to proteolytic cleavage by the proteases TACE and presenilin-2. The clipped-off intracellular domain (EpICD) was released from the membrane and moved into the nucleus, where it formed a DNA-bound complex with Lef-1 and β-catenin, which is a downstream effector of the Wnt pathway that is known to be involved in cell renewal and is commonly deregulated in cancer. Both EpCAM and EpICD were able to induce tumor formation in immunodeficient mice, and human colon carcinoma cells contained nuclear EpICD whereas normal colon cells did not. These results suggest that regulated intramembrane proteolysis may mediate an EpCAM signaling cascade from the cell membrane to the nucleus. — HP*

Nat. Cell Biol. 11, 162 (2009).

  • *Helen Pickersgill is a locum editor in Science's editorial department.

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