The DOI matches its Crossref record.
Phase separation of YAP mediated by coiled‐coil domain promotes hepatoblastoma proliferation via activation of transcription
Open accessAbstract
Aim and Background: Yes‐associated protein (YAP), a key transcriptional co‐activator associated with cell fate and tumor progression, has been reported to be a powerful driver of hepatoblastoma (HB). In this study, we investigated the mechanism underlying oncogenic role of YAP in HB. Methods: The expression of YAP in HB tissues was measured through WB and qRT‐PCR. The IHC and IF were performed to determine the distribution of YAP. The phase separation of YAP was proved by living cell imaging and FRAP experiment. The effect of YAP phase separation in HB cells in vitro an in vivo were tested using CCK8, flow cytometry, and xenograft tumors. Results: YAP was overexpressed and activated in HB. Nuclear YAP formed an active transcriptional site via LLPS to recruit the crucial transcription factor TEAD4. Thus, YAP phase separation facilitated transcription of oncogenic genes and subsequently mediated chemoresistance of HB. Mechanistically, the phase separation ability of YAP depends on the coiled‐coil domain, which is a typical phase separation domain. The electrostatic interactions and hydrophobic interactions within YAP are also vital to YAP phase separation. More importantly, YAP inhibitor verteporfin is potential treatment for HB and combination with cisplatin enhanced therapeutic efficacy. Conclusions: Highly expressed and active YAP exerts an oncogenic effect in HB via phase separation and provides new insights for the treatment of HB.
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YAP protein localises at liquid-liquid phase separation (LLPS) subcellular aggregates in hepatocytes.
“YAP protein localises at liquid–liquid phase separation (LLPS) subcellular aggregates in hepatocytes [48].”
From Mechanical stiffness orchestrates distinct regulation of MRTFs and YAP / TAZ transcriptional cofactors in hepatocytes (2026) · cites this paper as [48]
The section “YAP undergoes phase separation driven by the coiled-coil domain in HuH6” (page unavailable) reports YAP puncta in hepatoblastoma cells that were disrupted by an LLPS-disrupting treatment. The Discussion (page unavailable) also says endogenous YAP formed condensates in hepatoblastoma cells. These passages support the localization and LLPS point in that setting, but do not establish it for hepatocytes generally. (LLM, conf=0.86)
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Torres‐Ortiz, B. S., Pérez‐Calixto, D., Carretero‐Ortega, J., Guzman‐López, A. G., Pinto‐Dueñas, D. C., Hernández‐Juárez, M., Jiménez‐Escobar, A., Rodríguez‐Hernández, A., Díaz‐Bello, B., Serna‐Márquez, N., et al. (2026) · The FEBS Journal · doi:10.1111/febs.70570
Metadata
- Authors
- Mao, S., Liu, Q., Wu, H., Zhu, J., Xie, Y., Ma, J., Zhen, N., & Pan, Q.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Zhen, Ni
- Pan, Qiuhui
- Venue
- Journal of Gastroenterology and Hepatology
- Publisher
- Wiley
- Published
- 2023-04-13
- Volume
- 38
- Issue
- 8
- Pages
- 1398-1407
- ISSN
- 0815-9319 (ISSN-L)
- 1440-1746
- OpenAlex
- W4324019802
- Cited by
- 15
- References
- 0
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 4
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82072375, 82172357)
- Natural Science Foundation of Shanghai Municipality (22ZR1440400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- YAP, hepatoblastoma, phase separation, liquid-liquid phase separation, coiled-coil domain, TEAD4, transcriptional activation, oncogenic gene expression, chemoresistance, verteporfin, cisplatin combination therapy
- MeSH terms
- Verteporfin, TEA Domain Transcription Factors, Humans, Liver Neoplasms, Transcription Factors, Hepatoblastoma, Cell Line, Tumor, Cell Proliferation
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