High levels of ZEB transcription factors (ZEB1 and ZEB2) are correlated with a poor prognosis for solid tumors. Not only do these transcription factors modulate the metastasis potential of epithelial cancers, they have been linked with the acquisition of cancer stem cell properties. Therefore, downregulation of ZEB proteins have been suggested as a putative novel means for improving therapy for solid tumors.
Over the last years, more evidence is accumulating that ZEBs may play different and potentially opposing roles in blood-borne malignancies. In this project we aim to further investigate the role of ZEB1 and ZEB2 specifically in T cell lymphoblastic leukemia. Based on the literature and our preliminary data we hypothesize that ZEB1 and ZEB2 play antagonistic rather than synergistic roles in both human and mouse T-ALL. Using novel mouse models we will explore this antagonism in relevant in vivo settings.
Specifically, we aim to determine the interplay between Zeb1/2, their role in TGFβ signaling and cancer stem cell regulation that are very important aspects of T-ALL.