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液泡蛋白分选 4B,一种 ATP 酶蛋白,通过促进细胞分裂正向调节 NSCLC 的进展。

Vacuolar protein sorting 4B, an ATPase protein positively regulates the progression of NSCLC via promoting cell division.

机构信息

Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

出版信息

Mol Cell Biochem. 2013 Sep;381(1-2):163-71. doi: 10.1007/s11010-013-1699-2. Epub 2013 Jun 5.

DOI:10.1007/s11010-013-1699-2
PMID:23737133
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.

摘要

液泡蛋白分选 4B(VPS4B)是 ATP 酶家族蛋白的成员,在溶酶体依赖性降解中发挥关键作用。最近发现,VPS4B 可以通过促进 EGFR 的溶酶体依赖性降解来负调控乳腺癌的进展。然而,其他研究发现,VPS4B 还通过确保中心体和纺锤体组装的维持对细胞分裂和有丝分裂至关重要。因此,VPS4B 在癌症生物学中的作用仍存在争议。在这项研究中,我们分析了 VPS4B 在非小细胞肺癌(NSCLC)中的临床意义。通过 Western blot 分析了 8 对新鲜 NSCLC 组织中的 VPS4B 表达,并通过免疫组织化学分析了 105 个石蜡切片中的 VPS4B 表达。VPS4B 在 NSCLC 中高表达,与 NSCLC 的肿瘤大小、组织学分化、临床分期和 Ki-67 显著相关。此外,高 VPS4B 表达是 NSCLC 患者预后不良的独立预后因素。为了确定 VPS4B 是否可以调节 NSCLC 细胞的增殖,我们敲低了 VPS4B 的表达,并通过 Western blot、CCK8 和流式细胞术分析了 A549 NSCLC 细胞的增殖,结果表明 VPS4B 的缺失可以抑制细胞周期进程。这些数据表明,VPS4B 可能促进 NSCLC 的进展,是 NSCLC 治疗的生物靶点。

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