Erforschung der molekularen Grundlage des MIA-Proteins bei der Metastasierung im malignen Melanom

Institutions: Ruhr-Universität Bochum und Universitätsklinikum Essen
Applicants: Prof. Dr. Raphael Stoll und PD Dr. Iris Helfrich
Funding line:
First and Second Applications
FPLC-based protein purification

Melanoma inhibitory activity (MIA), an extracellular protein highly expressed by malignant melanoma cells, plays an important functional role in melanoma development, progression, and metastasis. After its secretion, MIA directly interacts with extracellular matrix proteins, such as fibronectin (FN). By this mechanism, MIA actively facilitates focal cell detachment from surrounding structures and strongly promotes tumour cell invasion and migration. Hence, the molecular understanding of MIA’s function provides a promising target for the development of new strategies in malignant melanoma therapy.

We describe for the first time the discovery of small molecules that are able to disrupt the MIA-FN complex by selectively binding to a new druggable pocket, which we could identify on MIA by structural analysis and fragment-based screening. Our findings may inspire novel drug discovery efforts aiming at a therapeutically effective treatment of melanoma by targeting MIA.