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Updated: Feb 4, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway
Le Bao1, Lei Yuan1, Pengfei Li1
1Department of Intervention, Xuzhou Cancer Hospital, Xuzhou Hospital Affiliated to Jiangsu University, Xuzhou, China.
Background/Aims:
The roles and related mechanisms of RNA binding protein FUS (fused in sarcoma/translocated in liposarcoma) are unclear in numerous cancers, including hepatocellular carcinoma (HCC).
Methods:
Quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, transwell migration and invasion, tumor spheres formation and in vivo tumor formation assays were used to examine the effects of FUS on HCC progression in HuH7 and MHCC97 cells. Additionally, transcriptome analysis based on RNA-sequencing data, qRT-PCR, western blots, luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays were used to explore the LATS1/2 (large tumor suppressor kinases 1/2)-related mechanisms contributing to FUS functions. Finally, qRT-PCR and western blot analysis were used to detect the levels of FUS and LATS1/2 in HCC and adjacent normal tissues, and the correlation between them in HCC tissues.
Results:
Overexpression of FUS decreased cell viability, migration, invasion and stemness. Moreover, FUS interacted and stabilized LATS1/2 stability, and thus promoted LATS1/2 expression and activated Hippo pathway. Finally, FUS and LAST1/2 levels were positively correlated and significantly down-regulated in HCC tissues.
Conclusion:
We demonstrate that FUS/LATS1/2 axis inhibits HCC progression via activating Hippo pathway.
Insights
Fused in sarcoma (FUS) protein suppresses hepatocellular carcinoma (HCC) progression by stabilizing LATS1/2, activating the Hippo pathway. FUS and LATS1/2 are downregulated in HCC tissues.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The role of the RNA-binding protein FUS (fused in sarcoma) in hepatocellular carcinoma (HCC) remains largely unknown.
- Understanding FUS's function is crucial for developing new therapeutic strategies against HCC.
Purpose of the Study:
- To investigate the role and underlying mechanisms of FUS in HCC progression.
- To explore the relationship between FUS, LATS1/2, and the Hippo pathway in HCC.
Main Methods:
- Utilized quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, migration, invasion, and tumor sphere formation assays.
- Conducted transcriptome analysis via RNA-sequencing, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays.
- Analyzed FUS and LATS1/2 expression levels in HCC and adjacent normal tissues.
Main Results:
- Overexpression of FUS inhibited HCC cell viability, migration, invasion, and stemness.
- FUS was found to interact with and stabilize LATS1/2, promoting its expression and activating the Hippo pathway.
- FUS and LATS1/2 levels were positively correlated and significantly downregulated in HCC tissues.
Conclusions:
- The FUS/LATS1/2 axis plays a critical role in inhibiting HCC progression.
- Activation of the Hippo pathway by FUS/LATS1/2 represents a potential therapeutic target for HCC.
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