Cooperative and exclusive functions of Hippo pathway effectors in hepatocarcinogenesis (B03)

• Subject Area: Pathology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314905040

Project B03 (Breuhahn/Weiler; Cooperative and exclusive functions of Hippo pathway effectors in hepatocarcinogenesis) follows the longstanding aim to identify the mechanisms of oncogenic Hippo-pathway disturbance. They have shown that the pathway effectors YAP and TAZ represent strong oncogenes with cooperative and overlapping but nonidentical functions; the project has demonstrated tumor cell intrinsic oncogenic mechanisms, such as stimulation of proliferation and induction of genomic instability, but it has recently also shown a protumorigenic YAP/TAZ-dependent extrinsic heterologous communication network acting on Kupffer cells and sinusoidal endothelial cells. In the next funding period these extrinsic functions of YAP and TAZ will be precisely dissected and their effects on HCC development will be determined by using spatial proteomics and transcriptomics as well as biochemical and cell-based analyses. Aim is to determine specific measures of antineoplastic intervention avoiding adverse effects of combined YAP/TAZ inhibition.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 209: Liver Cancer - New mechanistic and therapeutic concepts in a solid tumor model
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Professor Dr. Kai Breuhahn; Dr. Sofia Maria Elisabeth Weiler, since 7/2021