Fedor Berditchevski - Overview

Adhesive interactions with the extracellular matrix (ECM) constitute a basis for invasion of tumour cells into surrounding tissues and subsequent tumour dissemination. Cell surface proteins of the integrin superfamily act as major mediators of cell-ECM interactions. Furthermore, integrins function as a platform for the assembly of various types of signalling complexes, which regulate tumor cell growth and motility. We have been investigating how transmembrane proteins of the tetraspanin superfamily affect signalling function of integrin receptors. Tetraspanins is a large group of ubiquitously expressed four transmembrane domain proteins. Tetraspanins form multimeric complexes with various integrins, and it has been proposed that they regulate presentation and membrane compartmentalisation of integrin heterodimers. We are currently examining the function of two tetraspanins, CD151 and KAI-1/CD82, in the adhesion-dependent signalling mediated by the a3b1 integrin.

The interaction with CD151 is critical for the assembly of the ____-containing signalling complexes which include phosphatidylinositol 4-kinase (PI4-K). We have recently identified the regions in CD151 responsible for its association with a3b1 and PI4-K. In the ongoing experiments we are analysing the consequences on the expression of various CD151 mutants on tumor cell motility and adhesion-dependent signalling with a particular emphasis on the signalling events that are associated with cell migration.

The expression of the metastasis suppressor tetraspanin KAI-1/CD82 is down-regulated in a wide variety of epithelial malignancies. We have recently established that this tetraspanin is associated with the receptor type tyrosine kinases of the ErbB family. Further studies have shown that KAI-1/CD82 functions as a negative regulator of signalling mediated by the EGF receptor. Our current studies aim to establish whether or not KAI-1/CD82 is involved in coordinating signalling from other ErbB proteins and the a3b1_integrin.