Cells
with epithelial characteristics arise at multiple times and places
during normal development. Uncontrolled growth of epithelial cells,
however, can result in the development of carcinomas that account for
over 90% of malignant tumors in humans.
The main interest of this
clinically oriented research group is the analysis of gene alterations
affecting the cadherin/catenin cell adhesion and signalling complex in
human cancer.
E-cadherin typically connects epithelial cells, reducing
their invasion potential. We have been interested especially in gastric
and breast carcinomas as model systems for studying cell adhesion
molecules because here tumors are frequently seen that show reduced
homophilic cell-to-cell cohesion and invade adjacent tissues
preferentially as single cells (diffuse-type gastric and lobular breast
cancer). Obviously, in these tumors molecules responsible for
maintaining stable cell adhesion are lost or not functional.
We
made the groundbreaking observation that E-cadherin in diffuse-type
gastric cancer is mutated. Most importantly, the mutated cell adhesion
molecules are expressed at the cell surface but they are not
functionally active, resulting in a scattered ("diffuse")
appearance of the tumors.