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Vacuolar protein sorting 4B, an ATPase protein positively regulates the progression of NSCLC via promoting cell
Yifei Liu1, Liting Lv, Qun Xue
1Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Abstract:
Vacuolar protein sorting 4B (VPS4B), a member of ATPase family proteins, plays a crucial role in lysosome-dependent degradation. Recently, it was found that VPS4B could negatively regulate breast cancer progression through promoting lysosomal-dependent degradation for EGFR. Nevertheless, other studies found that VPS4B was also essential for cell division and mitosis through insuring the maintenance of centrosome and spindle assembly. Thus, the role of VPS4B in cancer biology remains under debate. In this study, we analyzed the clinical significance of VPS4B in NSCLC. The expression of VPS4B was evaluated by Western blot in 8 paired fresh NSCLC tissues and immunohistochemistry on 105 paraffin-embedded slices. VPS4B was highly expressed in NSCLC and significantly associated with NSCLCs tumor size, histological differentiation, clinical stage and Ki-67. Besides, high VPS4B expression was an independent prognostic factor for NSCLC patients' poor survival. To determine whether VPS4B could regulate the proliferation of NSCLC cells, we knocked down the expression of VPS4B and analyzed the proliferation of A549 NSCLC cells using Western blot, CCK8 and flow cytometry assays, which together indicated that loss of VPS4B could inhibit cell cycle progress. These data suggest that VPS4B may promote the progression of NSCLC and be a biotarget for NSCLCs therapy.
Insights
Vacuolar protein sorting 4B (VPS4B) promotes non-small cell lung cancer (NSCLC) progression. High VPS4B expression correlates with advanced NSCLC and poor survival, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Vacuolar protein sorting 4B (VPS4B) is an ATPase involved in lysosomal degradation.
- VPS4B's role in cancer is debated, with conflicting reports on its function in breast cancer and cell division.
Purpose of the Study:
- To investigate the clinical significance and functional role of VPS4B in non-small cell lung cancer (NSCLC).
Main Methods:
- Western blot analysis of VPS4B expression in NSCLC tissues.
- Immunohistochemistry on 105 NSCLC paraffin-embedded slices.
- VPS4B knockdown in A549 NSCLC cells followed by proliferation assays (Western blot, CCK8, flow cytometry).
Main Results:
- VPS4B was highly expressed in NSCLC tissues.
- High VPS4B expression correlated with larger tumor size, poor histological differentiation, advanced clinical stage, and high Ki-67 index.
- VPS4B expression was an independent prognostic factor for poor survival in NSCLC patients.
- VPS4B knockdown inhibited NSCLC cell proliferation and cell cycle progression.
Conclusions:
- VPS4B promotes NSCLC progression.
- VPS4B may serve as a potential biomarker and therapeutic target for NSCLC.
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