Project Details
Projekt
The role of the EMT-transcription factor Zeb1 in CAFs for metastatic colonisation and growth (B07)
Subject Area
Hematology, Oncology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 429280966
The microenvironment at metastatic target sites determines the success of disseminating tumour cells to establish a metastatic colony. In metastasis of pancreatic ductal adenocarcinoma (PDAC) cancer associated fibroblasts (CAFs) are forming a very heterogeneous tumour microenvironment. This is reflected by activation of the EMT-inducing transcription factor ZEB1 in only a subset of CAFs. We hypothesize that ZEB1 is a crucial determinant of CAF subtype specification and function that drives disease progression. We will identify and analyse different CAF subpopulations and the role of ZEB1 in the process of colonization. We apply transplantation and genetic mouse tumour models, scRNA sequencing, ex vivo organ slice microscopy and human PDAC organoid-CAF co-cultures to address these hypothesis. With our findings on specific CAF subtypes, we hope to identify new therapeutic approaches targeting protumourigenic functions of the microenvironment during colonization.
DFG Programme
CRC/Transregios
Subproject of
TRR 305:
Striking a moving target: From mechanisms of metastatic colonization to novel systemic therapies
Applicant Institution
Universität Regensburg
