Mathematisch-Naturwissenschaftliche Fakultät

Institut für Biowissenschaften

Fachgebiet: Molekularbiologie

Betreuer: Prof. Dr. Brigitte M. Pützer

Diplom-Biophysiker Stephan Marquardt
(e-mail: )

Establishment of the E2F1-Interactome with Metastasis-relevant Factors by Integrating Bioinformatics and Experimental Methods

The transcription factor E2F1 is integrated into a highly complex gene regulatory network and is responsible for a multitude of cellular fates via transactivating its target genes involved in numerous molecular processes. Consequently, E2F1 represents as a key factor for epithelial-mesenchymal transition (EMT), the prerequisite for invasive proliferation and metastasis.

By intensive literature and database research we constructed a comprehensive map of interactions around E2F1 with regulators, cofactors and target genes to better understand the ambivalent behaviour of E2F1 in the cell.

The subsequent bioinformatics analysis of this map by using systems biology parameters and clinical-molecular data of a bladder cancer and a breast cancer model lead to identification of tumour-specific molecular signatures of E2F1-driven EMT. These signatures were validated experimentally as well as on patient data.

To characterize the interactome of two players of the signatures, E2F1 and TGFβ, I applied database research and bioinformatics analyses revealing numerous common EMT-relevant target genes that have an impact on patient survival of both cancer types. These factors might be suitable as tumour markers or targets for combination therapy.