CRKL enhances YAP signaling through binding and JNK/JUN pathway activation in liver cancer
The Hippo pathway transducers yes-associated protein (YAP) and WW-domain containing transcription regulator 1 (WWTR1/TAZ) are key regulators of liver tumorigenesis, promoting tumor formation and progression. Although the first inhibitors are in clinical trials, targeting the relevant upstream regula...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
5 August 2024
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| In: |
International journal of molecular sciences
Year: 2024, Jahrgang: 25, Heft: 15, Pages: 1-18 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms25158549 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms25158549 Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/25/15/8549 
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| Verfasserangaben: | Marie C. Wesener, Sofia M. E. Weiler, Michaela Bissinger, Tobias F. Klessinger, Fabian Rose, Sabine Merker, Marcin Luzarowski, Thomas Ruppert, Barbara Helm, Ursula Klingmüller, Peter Schirmacher and Kai Breuhahn |
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| 100 | 1 | |a Wesener, Marie C. |d 1998- |e VerfasserIn |0 (DE-588)1362628379 |0 (DE-627)1921645660 |4 aut | |
| 245 | 1 | 0 | |a CRKL enhances YAP signaling through binding and JNK/JUN pathway activation in liver cancer |c Marie C. Wesener, Sofia M. E. Weiler, Michaela Bissinger, Tobias F. Klessinger, Fabian Rose, Sabine Merker, Marcin Luzarowski, Thomas Ruppert, Barbara Helm, Ursula Klingmüller, Peter Schirmacher and Kai Breuhahn |
| 246 | 1 | |i Titel des special issue |a Liver cancer 3.0 | |
| 264 | 1 | |c 5 August 2024 | |
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| 520 | |a The Hippo pathway transducers yes-associated protein (YAP) and WW-domain containing transcription regulator 1 (WWTR1/TAZ) are key regulators of liver tumorigenesis, promoting tumor formation and progression. Although the first inhibitors are in clinical trials, targeting the relevant upstream regulators of YAP/TAZ activity could prove equally beneficial. To identify regulators of YAP/TAZ activity in hepatocarcinoma (HCC) cells, we carried out a proximity labelling approach (BioID) coupled with mass spectrometry. We verified CRK-like proto-oncogene adaptor protein (CRKL) as a new YAP-exclusive interaction partner. CRKL is highly expressed in HCC patients, and its expression is associated with YAP activity as well as poor survival prognosis. In vitro experiments demonstrated CRKL-dependent cell survival and the loss of YAP binding induced through actin disruption. Moreover, we delineated the activation of the JNK/JUN pathway by CRKL, which promoted YAP transcription. Our data illustrate that CRKL not only promoted YAP activity through its binding but also through the induction of YAP transcription by JNK/JUN activation. This emphasizes the potential use of targeting the JNK/JUN pathway to suppress YAP expression in HCC patients. | ||
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| 700 | 1 | |a Bissinger, Michaela |e VerfasserIn |0 (DE-588)1071099426 |0 (DE-627)825602807 |0 (DE-576)432961720 |4 aut | |
| 700 | 1 | |a Klessinger, Tobias F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rose, Fabian |d 1993- |e VerfasserIn |0 (DE-588)1246208636 |0 (DE-627)1778215238 |4 aut | |
| 700 | 1 | |a Merker, Sabine |e VerfasserIn |0 (DE-588)103825017X |0 (DE-627)756832381 |0 (DE-576)392231964 |4 aut | |
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| 700 | 1 | |a Helm, Barbara |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Breuhahn, Kai |d 1969- |e VerfasserIn |0 (DE-588)122803329 |0 (DE-627)082164959 |0 (DE-576)293427364 |4 aut | |
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