Colorectal cancer (CRC) is a frequently lethal disease with very heterogeneous outcomes and drug responses. The most aggressive subtype of CRC, consensus molecular subtype 4 (CMS4), shows the worst overall survival and a clear presence of an EMT (Epithelial-Mesenchymal Transition)-like expression signature. EMT is a physiological process, in which well-polarized epithelial cells lose their cell-cell contacts and acquire the motile-migratory properties of mesenchymal cells. EMT is a reversible process orchestrated by a network of transcription factors leading to cancer cell invasion and enhanced cell dissemination.
ZEB1 & ZEB2 are EMT-inducing transcription factors highly upregulated in the CMS4 group. In this research project, we try to further elucidate the mechanism of ZEB-driven EMT in the malignant development of CRC and the functional role on several characteristics including proliferation, migration, invasion, aggregation, therapy resistance and cancer stem cells. Colorectal cancer models will be used to identify drugable targets able to interfere with ZEB-mediated EMT in CRC.