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热休克蛋白 10 家族成员 1 亚基 8 通过调控 α-肌动蛋白和 β-微管蛋白的表达促进人食管鳞癌细胞的迁移和侵袭

Chaperonin-containing T‑complex protein 1 subunit 8 promotes cell migration and invasion in human esophageal squamous cell carcinoma by regulating α-actin and β-tubulin expression.

机构信息

Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated with Sixth People's Hospital, Shanghai 200233, P.R China.

Department of Orthopedics, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai 201300, P.R China.

出版信息

Int J Oncol. 2018 Jun;52(6):2021-2030. doi: 10.3892/ijo.2018.4335. Epub 2018 Mar 27.

Abstract

The chaperonin-containing T‑complex protein 1 (CCT) has eight subunits, CCT 1-8, which are dysregulated in several types of cancer. To determine how subunit 8 (CCT8) influences the development of esophageal squamous cell carcinoma (ESCC), immunohistochemistry and western blot analysis were performed on 128 ESCC samples in the present study to measure the expression of CCT8. The prognostic value of CCT8 was analyzed using univariate and multivariate survival analyses. CCT8 knockdown in ESCC cells was performed and subsequently, the migration and invasion of ESCC cells was assessed. The results of immunohistochemistry and western blot analysis of ESCC tissue indicated that the expression of CCT8 in tumor tissues from patients with lymph node metastasis (LNM) was high whereas its expression in tissues from those without LNM was low. In addition, the overall survival rate of patients with high CCT8 expression was poor. It was demonstrated that CCT8 influenced the migration and invasion of ESCC cells by regulating α-actin and β-tubulin. Following CCT8 knockdown, cells were treated with cisplatin; it was demonstrated that α-actin and β-tubulin were downregulated and that cell apoptosis was enhanced. These data confirm that α-actin and β-tubulin are regulated by CCT8, and that increased CCT8 expression is associated with poor patient prognosis and cisplatin resistance in ESCC.

摘要

含 chaperonin 的 T 复合物蛋白 1(CCT)包含 8 个亚基,CCT1-8,在几种类型的癌症中失调。为了确定亚基 8(CCT8)如何影响食管鳞状细胞癌(ESCC)的发展,本研究对 128 例 ESCC 样本进行了免疫组织化学和 Western blot 分析,以测量 CCT8 的表达。使用单因素和多因素生存分析分析了 CCT8 的预后价值。在 ESCC 细胞中进行 CCT8 敲低,随后评估 ESCC 细胞的迁移和侵袭。ESCC 组织的免疫组织化学和 Western blot 分析结果表明,有淋巴结转移(LNM)的患者肿瘤组织中 CCT8 的表达较高,而无 LNM 的患者肿瘤组织中 CCT8 的表达较低。此外,高 CCT8 表达患者的总生存率较差。结果表明,CCT8 通过调节α-肌动蛋白和β-微管蛋白影响 ESCC 细胞的迁移和侵袭。CCT8 敲低后,用顺铂处理细胞,结果表明α-肌动蛋白和β-微管蛋白下调,细胞凋亡增强。这些数据证实,α-肌动蛋白和β-微管蛋白受 CCT8 调节,CCT8 表达增加与 ESCC 患者预后不良和顺铂耐药有关。

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