FBXW8-mediated degradation of PPT1 suppresses epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.F-box and WD repeat domain-containing 8 (FBXW8) acts as a tumor suppressor in hepatocellular carcinoma (HCC) by degrading palmitoyl-protein thioesterase 1 (PPT1), inhibiting cancer progression and metastasis.
Area Of Science
- Molecular Biology
- Oncology
- Biochemistry
Background
- Hepatocellular carcinoma (HCC) is a major cause of cancer mortality, with poorly understood mechanisms driving its progression.
- Dysregulation of the ubiquitin-proteasome system (UPS) is implicated in cancer, but its specific role in HCC pathogenesis requires further elucidation.
Purpose Of The Study
- To identify novel tumor suppressors in HCC and elucidate their mechanisms of action.
- To investigate the role of F-box and WD repeat domain-containing 8 (FBXW8) in HCC development and metastasis.
Main Methods
- In vitro and in vivo HCC models were utilized to assess FBXW8's function.
- Proteomic analysis identified FBXW8's substrate, palmitoyl-protein thioesterase 1 (PPT1).
- Correlation between PPT1 expression, EMT markers, and clinical prognosis in HCC patients was analyzed.
Main Results
- FBXW8 depletion enhanced HCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- FBXW8 targets PPT1 for degradation, and elevated PPT1 expression correlates with poor HCC prognosis and EMT activation.
- PPT1 promotes EMT by upregulating transcription factors like SNAIL and ZEB1, while FBXW8-mediated PPT1 degradation inhibits metastasis.
Conclusions
- The FBXW8-PPT1 axis is a critical regulator of HCC progression and metastasis, linking UPS function to cancer pathogenesis.
- Targeting PPT1 or restoring FBXW8 activity presents a potential therapeutic strategy for HCC.
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