Structural and Functional Characterization of the RAI2 Protein

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In most cancer patients, mortality is linked to metastasis. In the course of our proceeding DFG-funded project at UKE (DFG 5/2012-4/2015) loss of retinoic acid-induced 2 (RAI2) gene expression in primary breast tumors was indentified as a novel genetic determinant associated especially with poor prognosis and early metastatic spread of hormone receptor positive breast tumours. To start the functional characterization of the RAI2 protein, scientific collaboration was initiated with the Wilmanns group at the Hamburg unit of the EMBL. These joint efforts of the research teams at UKE and EMBL led to first insight into the previously completely uncharacterized functions of the RAI2 protein. We were able to show that the RAI2 protein can act as a transcriptional co-regulator that sustains the differentiation of luminal breast cancer cells, which leads to a more aggressive phenotype of tumor cells. In the proposed research project, we want to continue our successful collaboration and deepen the functional characterization of the RAI2 protein by analyzing the interactome and the molecular structure of this still poorly characterized protein. This will help to approach our long-term goal to explore whether the RAI2 protein could represent a drugable target for the development of novel therapeutic strategies or for the enhancement of existing ones for the treatment of cancer patients.