Kindlin-1 promotes mitophagy by inhibiting PINK1 degradation to enhance hepatocellular carcinoma progression and modulates sensitivity to donafenib
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View abstract on PubMed
Summary
This summary is machine-generated.Kindlin-1 promotes hepatocellular carcinoma (HCC) progression by enhancing mitophagy via PINK1 stabilization. Inhibiting Kindlin-1 or mitophagy boosts donafenib
Area Of Science
- Molecular Biology
- Oncology
- Cellular Biology
Background
- Mitophagy is crucial for mitochondrial homeostasis but its role in hepatocellular carcinoma (HCC) progression and drug response is not fully understood.
- Kindlin-1, an adhesion protein, is implicated in aggressive phenotypes of solid tumors by regulating integrin function.
Purpose Of The Study
- To investigate the clinical significance and cellular functions of Kindlin-1 in HCC.
- To determine Kindlin-1's role in HCC progression, mitophagy, and sensitivity to donafenib.
- To explore Kindlin-1's impact on HCC cell proliferation, metastasis, and its therapeutic potential.
Main Methods
- Assessed Kindlin-1 expression and prognosis in HCC tissues.
- Utilized cell proliferation, metastasis, and tumorigenesis assays.
- Employed RNA sequencing, Co-IP, mass spectrometry, and in vitro/in vivo mitophagy assessments.
Main Results
- Kindlin-1 is highly expressed in HCC and correlates with poor prognosis.
- Kindlin-1 promotes HCC cell proliferation by stabilizing PINK1, enhancing mitophagy.
- Inhibiting Kindlin-1 or mitophagy synergistically enhances donafenib's anti-tumor effects.
Conclusions
- Kindlin-1 drives HCC progression by regulating mitophagy via the PINK1/Parkin pathway.
- Targeting Kindlin-1 offers a potential strategy to improve donafenib efficacy in HCC treatment.
- This study provides novel insights into HCC pathogenesis and therapeutic interventions.
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