Incurable metastasis still remains the major cause of death among women diagnosed with breast cancer. Metastasis is regulated by the activation of genes that promote and by the inactivation of genes that normally prevent this process. There are meanwhile comprehensive molecular profiles available from metastatic breast cancer, providing extensive lists for novel candidate genes for metastatic spread. The function of most of these genes is still unknown, however, as well as their role in metastatic spread. Recently, miRNAs have been added as crucial regulators of metastatic spread, and corresponding profiles from metastatic breast cancer are available as well.
Acquiring metastatic abilities is associated with a process known as epithelial-to-mesenchymal transition (EMT). This switch in cell phenotype is simultaneously connected to acquiring a cancer stem cell-like phenotype, which is in accordance with the CSCs being considered as the pool of metastatic cells within a tumor.
The subproject aims at a systematic functional genomics approach, analyzing a set of >100 candidate genes and miRNAs from available molecular profiles of metastatic breast cancers in order to identify new crucial regulators of metastasis formation and EMT. The data may not only provide valuable starting points for therapeutic strategies aiming at the suppression of metastatic spread and EMT, but also improve the understanding of the properties of cancer stem cells.