TRAP1 regulates proliferation, mitochondrial function, and has prognostic significance in NSCLC

Area of Science:

• Oncology
• Molecular Biology
• Mitochondrial Biology

Background:

• TNF receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein implicated in drug resistance and apoptosis evasion in various cancers.
• Its role in non-small cell lung cancer (NSCLC) remains largely unexplored.

Purpose of the Study:

• To investigate the functional role of TRAP1 in NSCLC cell proliferation, survival, apoptosis, and mitochondrial function.
• To evaluate the prognostic significance of TRAP1 expression in NSCLC patients.

Main Methods:

• TRAP1 ablation using knockdown techniques.
• Assessment of cell proliferation, clonogenic survival, and apoptosis (flow cytometry, immunoblotting for cleaved PARP, caspase-9, caspase-3).
• Evaluation of mitochondrial function (ATP production, mitochondrial membrane potential via TMRM uptake) and morphology.
• Immunohistochemical analysis of TRAP1 expression in NSCLC patient tissues for prognostic value.

Main Results:

• TRAP1 knockdown significantly reduced NSCLC cell growth and survival.
• Downregulation of TRAP1 impaired mitochondrial functions, including ATP production and membrane potential, without altering mitochondrial density or morphology.
• The impact of TRAP1 silencing on apoptosis was context-dependent.
• High TRAP1 expression was significantly associated with an increased risk of disease recurrence in NSCLC patients (univariate and multivariate analyses).

Conclusions:

• TRAP1 plays a critical role in regulating NSCLC cell proliferation, survival, and mitochondrial function.
• TRAP1 expression serves as a significant prognostic biomarker for disease recurrence in NSCLC.