The cell polarity protein MPP5/PALS1 controls the subcellular localization of the oncogenes YAP and TAZ in liver cancer
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 combinat...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
14 January 2025
|
| In: |
International journal of molecular sciences
Year: 2025, Volume: 26, Issue: 2, Pages: 1-17 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms26020660 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms26020660 Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/26/2/660 
|
| Author Notes: | Marcell Tóth, Shan Wan, Jennifer Schmitt, Patrizia Birner, Teng Wei, Fabian von Bubnoff, Carolina de la Torre, Stefan Thomann, Federico Pinna, Peter Schirmacher, Sofia Maria Elisabeth Weiler and Kai Breuhahn |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1932801480 | ||
| 003 | DE-627 | ||
| 005 | 20251209005841.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250807s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms26020660 |2 doi | |
| 035 | |a (DE-627)1932801480 | ||
| 035 | |a (DE-599)KXP1932801480 | ||
| 035 | |a (OCoLC)1559703991 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Tóth, Marcell |d 1990- |e VerfasserIn |0 (DE-588)1171731361 |0 (DE-627)1040674186 |0 (DE-576)513819568 |4 aut | |
| 245 | 1 | 4 | |a The cell polarity protein MPP5/PALS1 controls the subcellular localization of the oncogenes YAP and TAZ in liver cancer |c Marcell Tóth, Shan Wan, Jennifer Schmitt, Patrizia Birner, Teng Wei, Fabian von Bubnoff, Carolina de la Torre, Stefan Thomann, Federico Pinna, Peter Schirmacher, Sofia Maria Elisabeth Weiler and Kai Breuhahn |
| 246 | 1 | |i Titel des übergeordneten Special issue |a Pathogenesis and molecular treatment of primary liver cancer | |
| 264 | 1 | |c 14 January 2025 | |
| 300 | |b Illustrationen, Diagramme | ||
| 300 | |a 17 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 07.08.2025 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a apical polarity | |
| 650 | 4 | |a Crumbs complex | |
| 650 | 4 | |a HCC | |
| 650 | 4 | |a Hippo pathway | |
| 650 | 4 | |a tumor-suppressor gene | |
| 700 | 1 | |a Wan, Shan |e VerfasserIn |0 (DE-588)1143865383 |0 (DE-627)1003415520 |0 (DE-576)495184748 |4 aut | |
| 700 | 1 | |a Schmitt, Jennifer |e VerfasserIn |0 (DE-588)1343726352 |0 (DE-627)1903984343 |4 aut | |
| 700 | 1 | |a Birner, Patrizia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wei, Teng |d 1992- |e VerfasserIn |0 (DE-588)1188763237 |0 (DE-627)166768728X |4 aut | |
| 700 | 1 | |a Bubnoff, Fabian von |e VerfasserIn |4 aut | |
| 700 | 1 | |a Torre, Carolina de la |d 1985- |e VerfasserIn |0 (DE-588)1122355831 |0 (DE-627)875651283 |0 (DE-576)481254137 |4 aut | |
| 700 | 1 | |a Thomann, Stefan |d 1987- |e VerfasserIn |0 (DE-588)1072011913 |0 (DE-627)826775705 |0 (DE-576)433478195 |4 aut | |
| 700 | 1 | |a Pinna, Federico |e VerfasserIn |0 (DE-588)1073978087 |0 (DE-627)830090509 |0 (DE-576)435462369 |4 aut | |
| 700 | 1 | |a Schirmacher, Peter |d 1961- |e VerfasserIn |0 (DE-588)1020440112 |0 (DE-627)691221197 |0 (DE-576)360427448 |4 aut | |
| 700 | 1 | |a Weiler, Sofia Maria Elisabeth |e VerfasserIn |0 (DE-588)1137854960 |0 (DE-627)89512887X |0 (DE-576)49177088X |4 aut | |
| 700 | 1 | |a Breuhahn, Kai |d 1969- |e VerfasserIn |0 (DE-588)122803329 |0 (DE-627)082164959 |0 (DE-576)293427364 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d Basel : Molecular Diversity Preservation International, 2000 |g 26(2025), 2, Artikel-ID 660, Seite 1-17 |h Online-Ressource |w (DE-627)316340715 |w (DE-600)2019364-6 |w (DE-576)281194653 |x 1422-0067 |7 nnas |a The cell polarity protein MPP5/PALS1 controls the subcellular localization of the oncogenes YAP and TAZ in liver cancer |
| 773 | 1 | 8 | |g volume:26 |g year:2025 |g number:2 |g elocationid:660 |g pages:1-17 |g extent:17 |a The cell polarity protein MPP5/PALS1 controls the subcellular localization of the oncogenes YAP and TAZ in liver cancer |
| 856 | 4 | 0 | |u https://doi.org/10.3390/ijms26020660 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |7 0 |
| 856 | 4 | 0 | |u https://www.mdpi.com/1422-0067/26/2/660 |x Verlag |z kostenfrei |3 Volltext |7 0 |
| 951 | |a AR | ||
| 992 | |a 20250807 | ||
| 993 | |a Article | ||
| 994 | |a 2025 | ||
| 998 | |g 122803329 |a Breuhahn, Kai |m 122803329:Breuhahn, Kai |d 910000 |d 912000 |d 50000 |e 910000PB122803329 |e 912000PB122803329 |e 50000PB122803329 |k 0/910000/ |k 1/910000/912000/ |k 0/50000/ |p 12 |y j | ||
| 998 | |g 1137854960 |a Weiler, Sofia Maria Elisabeth |m 1137854960:Weiler, Sofia Maria Elisabeth |d 910000 |d 912000 |e 910000PW1137854960 |e 912000PW1137854960 |k 0/910000/ |k 1/910000/912000/ |p 11 | ||
| 998 | |g 1020440112 |a Schirmacher, Peter |m 1020440112:Schirmacher, Peter |d 910000 |d 912000 |e 910000PS1020440112 |e 912000PS1020440112 |k 0/910000/ |k 1/910000/912000/ |p 10 | ||
| 998 | |g 1072011913 |a Thomann, Stefan |m 1072011913:Thomann, Stefan |d 910000 |d 912000 |e 910000PT1072011913 |e 912000PT1072011913 |k 0/910000/ |k 1/910000/912000/ |p 8 | ||
| 998 | |g 1122355831 |a Torre, Carolina de la |m 1122355831:Torre, Carolina de la |d 60000 |d 60200 |d 60210 |e 60000PT1122355831 |e 60200PT1122355831 |e 60210PT1122355831 |k 0/60000/ |k 1/60000/60200/ |k 2/60000/60200/60210/ |p 7 | ||
| 998 | |g 1171731361 |a Tóth, Marcell |m 1171731361:Tóth, Marcell |d 50000 |e 50000PT1171731361 |k 0/50000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1932801480 |e 4754924630 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"relHost":[{"title":[{"title":"International journal of molecular sciences","title_sort":"International journal of molecular sciences"}],"origin":[{"publisher":"Molecular Diversity Preservation International","dateIssuedDisp":"2000-","dateIssuedKey":"2000","publisherPlace":"Basel"}],"note":["Gesehen am 17.09.20"],"physDesc":[{"extent":"Online-Ressource"}],"part":{"volume":"26","text":"26(2025), 2, Artikel-ID 660, Seite 1-17","year":"2025","pages":"1-17","extent":"17","issue":"2"},"id":{"eki":["316340715"],"issn":["1422-0067","1661-6596"],"zdb":["2019364-6"]},"language":["eng"],"titleAlt":[{"title":"IJMS"}],"disp":"The cell polarity protein MPP5/PALS1 controls the subcellular localization of the oncogenes YAP and TAZ in liver cancerInternational journal of molecular sciences","recId":"316340715","type":{"media":"Online-Ressource","bibl":"periodical"},"pubHistory":["1.2000 -"]}],"note":["Gesehen am 07.08.2025"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"eki":["1932801480"],"doi":["10.3390/ijms26020660"]},"physDesc":[{"extent":"17 S.","noteIll":"Illustrationen, Diagramme"}],"titleAlt":[{"title":"Pathogenesis and molecular treatment of primary liver cancer"}],"language":["eng"],"title":[{"title_sort":"cell polarity protein MPP5/PALS1 controls the subcellular localization of the oncogenes YAP and TAZ in liver cancer","title":"The cell polarity protein MPP5/PALS1 controls the subcellular localization of the oncogenes YAP and TAZ in liver cancer"}],"recId":"1932801480","name":{"displayForm":["Marcell Tóth, Shan Wan, Jennifer Schmitt, Patrizia Birner, Teng Wei, Fabian von Bubnoff, Carolina de la Torre, Stefan Thomann, Federico Pinna, Peter Schirmacher, Sofia Maria Elisabeth Weiler and Kai Breuhahn"]},"origin":[{"dateIssuedDisp":"14 January 2025","dateIssuedKey":"2025"}],"person":[{"family":"Tóth","given":"Marcell","display":"Tóth, Marcell","role":"aut"},{"given":"Shan","display":"Wan, Shan","family":"Wan","role":"aut"},{"family":"Schmitt","given":"Jennifer","display":"Schmitt, Jennifer","role":"aut"},{"role":"aut","display":"Birner, Patrizia","given":"Patrizia","family":"Birner"},{"given":"Teng","display":"Wei, Teng","family":"Wei","role":"aut"},{"family":"Bubnoff","given":"Fabian von","display":"Bubnoff, Fabian von","role":"aut"},{"role":"aut","family":"Torre","display":"Torre, Carolina de la","given":"Carolina de la"},{"family":"Thomann","given":"Stefan","display":"Thomann, Stefan","role":"aut"},{"family":"Pinna","given":"Federico","display":"Pinna, Federico","role":"aut"},{"role":"aut","family":"Schirmacher","given":"Peter","display":"Schirmacher, Peter"},{"display":"Weiler, Sofia Maria Elisabeth","given":"Sofia Maria Elisabeth","family":"Weiler","role":"aut"},{"role":"aut","given":"Kai","display":"Breuhahn, Kai","family":"Breuhahn"}]} | ||
| SRT | |a TOTHMARCELCELLPOLARI1420 | ||