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Project B4: Exploiting tumor-stroma Hedgehog signal transduction heterogeneity

Participant:

Prof. Dr. Matthias Lauth
Institute of Molecular Biology and Tumor Research
Center for Tumor- and Immune Biology (ZTI)
Philipps-Universität Marburg

Project aims:

The activity of canonical Hedgehog (Hh) signaling and its GLI transcription factors is asymmetrically distributed in pancreatic ductal adenocarcinoma (PDAC). While high-level tumor-restraining canonical Hh signaling is associated with the mesenchymal stroma, lower-level oncogenic non-canonical GLI activation can be found in the epithelial tumor cell compartment. Therefore, from a translational point of view, one should aim at retaining stromal Hh activity, while blocking its activity in the cancer cell compartment. We hypothesize that the compartment-specific Hh signaling cascades might utilize different intracellular regulators, therefore allowing for selective targeting of non-canonical versus canonical Hh signaling. In this project, we want to exploit and investigate this signal transduction heterogeneity and verify its translational validity in various in vitro and in vivo PDAC models.

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