Targeting pathways involved in ZEB1-driven EMT in an aggressive subtype of colorectal cancer

Colorectal cancer is a frequently lethal disease with very heterogeneous outcomes and drug
responses. ZEB1 is a transcription factor controlling the epithelial-to-mesenchymal transition
(EMT) process, a developmental program reactivated during cancer progression. Cancer cells
undergoing EMT acquire the capacity to disseminate, resist cell death and anticancer
drugs/therapy and act as a reservoir to replenish the cells. Therefore, ZEB1-mediated EMT
becomes a target of prime interest to develop novel and improved anticancer therapies.
This PhD aims to further explore the signaling pathways involved in ZEB1-mediated cancer
initiation/progression to gain insights in the mechanisms used by ZEB1 to promote malignant
progression and to identify putative drugable nodes and specific biomarkers that can be used to
target aggressive subtypes of CRC. This will be done by altering the ZEB1 expression in human CRC
cellular models, analyzing characteristics driving malignant behavior, followed by study of
associated differential signaling and mapping the genome-wide binding sites. A second aim is to
screen a siRNA and small compound library with a highly-sensitive EMT-sensor to identify
proteins/pathways/compounds that can prevent or revert ZEB1-mediated CRC progression.