Technical University of MunichKlinikum rechts der Isar Munich

 

Institut für Pathologie

Trogerstrasse 18

D-81675 München

The lab page of Karl-Friedrich Becker

 

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Cells expressing mutant E-cadherin show markedly reduced cell adhesion

E-cadherin mutations result in cell scattering

 

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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.The cell adhesion molecule E-cadherin typically connects epithelial cells. In diffuse-type gastric cancer E-cadherin is mutated, resulting in a scattered growth of the tumor cells.

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.


Our main projects currently are:
  • New: clinical proteomics

We succeeded in the isolation of intact, soluble and immunoreactive proteins from formalin fixed tissues routinely processed in our hospital. We are using protein microarrays to quantify known molecular markers. Our technology can also be used to identify novel disease markers in high throughput and in an automatic fashion. More...

Our E-cadherin mutation-specific monoclonal antibodies are optimal means for diagnosis and therapy of gastric cancer patients.

Epithelial-mesenchymal-transition is crucial for tumor cell invasion and metastasis. Thus, elucidation of the mechanisms responsible for this process and evaluating the clinical significance as planned in our study may lead to the design of novel anti-invasive strategies for therapeutic intervention.

  • Hypoxia and epithelial-mesenchymal-transition

Low levels of oxygen (hypoxia) is known to be involved in invasion and metastasis of human tumors. The mechanisms by which hypoxia increases the invasion potential of tumor cells, however, are not known in every detail. My group has been awarded a research grant from the German research organization (DFG) to elucidate whether epithelial-mesenchymal-transition regulators play a role in hypoxia mediated increase in invasion and metastasis. This project is a close collaboration with the Clinic of Nuclear Medicine from the Technical University of Munich. More information will follow soon.

 


© 2003-2006 Dr. Karl-Friedrich Becker,

Institut für Pathologie, TU München

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slide show

E-cadherin mutations and

cell biology

 

Here are our Milestones