Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Tóth, M; Wan, S; Schmitt, J; Birner, P; Wei, T; von, Bubnoff, F; de, la, Torre, C; Thomann, S; Pinna, F; Schirmacher, P; Weiler, SME; Breuhahn, K.
The Cell Polarity Protein MPP5/PALS1 Controls the Subcellular Localization of the Oncogenes YAP and TAZ in Liver Cancer.
Int J Mol Sci. 2025; 26(2):
Doi: 10.3390/ijms26020660
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- Führende Autor*innen der Med Uni Graz
- Toth Marcell
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- Abstract:
- The oncogenes yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are potent liver oncogenes. Because gene mutations cannot fully explain their nuclear enrichment, we aim to understand which mechanisms cause YAP/TAZ activation in liver cancer cells. The combination of proteomics and functional screening identified numerous apical cell polarity complex proteins interacting with YAP and TAZ. Co-immunoprecipitation (Co-IP) experiments confirmed that membrane protein palmitoylated 5 (MPP5; synonym: PALS1) physically interacts with YAP and TAZ. After removing different MPP5 protein domains, Co-IP analyses revealed that the PDZ domain plays a crucial role in YAP binding. The interaction between YAP and MPP5 in the cytoplasm of cancer cells was demonstrated by proximity ligation assays (PLAs). In human hepatocellular carcinoma (HCC) tissues, a reduction in apical MPP5 expression was observed, correlating with the nuclear accumulation of YAP and TAZ. Expression data analysis illustrated that MPP5 is inversely associated with YAP/TAZ target gene signatures in human HCCs. Low MPP5 levels define an HCC patient group with a poor clinical outcome. In summary, MPP5 facilitates the nuclear exclusion of YAP and TAZ in liver cancer. This qualifies MPP5 as a potential tumor-suppressor gene and explains how changes in cell polarity can foster tumorigenesis.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Liver Neoplasms - metabolism, genetics, pathology
- Transcription Factors - metabolism, genetics
- Adaptor Proteins, Signal Transducing - metabolism, genetics
- Carcinoma, Hepatocellular - metabolism, genetics, pathology
- YAP-Signaling Proteins - metabolism, genetics
- Transcriptional Coactivator with PDZ-Binding Motif Proteins - metabolism
- Membrane Proteins - metabolism, genetics
- Cell Polarity - genetics
- Cell Line, Tumor - administration & dosage
- Trans-Activators - metabolism, genetics
- Cell Nucleus - metabolism
- Protein Binding - administration & dosage
- Gene Expression Regulation, Neoplastic - administration & dosage
- Acyltransferases - metabolism, genetics
- Oncogenes - administration & dosage
- Find related publications in this database (Keywords)
- tumor-suppressor gene
- apical polarity
- Crumbs complex
- HCC
- Hippo pathway