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TMEM176A 通过抑制 ERK 信号通路在胰腺癌中发挥肿瘤抑制基因的作用。

TMEM176A acts as a tumor suppressor gene in pancreatic cancer by inhibiting ERK signaling.

机构信息

Department of General Surgery, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.

School of Public Health, Xiangnan University, Chenzhou, Hunan 423000, China.

出版信息

Discov Med. 2020 Nov-Dec;30(161):145-153.

Abstract

BACKGROUND

Pancreatic cancer is the 7th leading cause of cancer-related death worldwide. Aberrant expressions of transmembrane 176A (TMEM176A) were found in multiple cancer types. However, the expression and function of TMEM176A remain unclear in pancreatic cancer.

MATERIALS AND METHODS

Immunohistochemistry, flow cytometry, western blot, and transwell were applied on investigating samples from pancreatic cancer patients and pancreatic cancer cell lines.

RESULTS

Analysis based on the TCGA database showed that a high level of TMEM176A was associated with a better relapse-free survival rate (P = 0.012). Further, the results of tissue microarray showed patients with a high level of TMEM176A were associated with lymph node metastasis (P = 0.045) and a better overall survival rate (P = 0.032). Overexpression of TMEM176A in Capan-1 and PANC-1 cells suppressed cell proliferation, cell invasion, and migration, and induced apoptosis in pancreatic cancer cells. TMEM176A suppressed ERK signaling in pancreatic cancer.

CONCLUSION

TMEM176A suppresses the growth and migration of pancreatic cancer cells by inhibiting ERK signaling.

摘要

背景

胰腺癌是全球第七大癌症相关死亡原因。跨膜蛋白 176A(TMEM176A)在多种癌症类型中存在异常表达。然而,TMEM176A 在胰腺癌中的表达和功能尚不清楚。

材料与方法

应用免疫组织化学、流式细胞术、Western blot 和 Transwell 检测来自胰腺癌患者和胰腺癌细胞系的样本。

结果

基于 TCGA 数据库的分析表明,TMEM176A 水平高与无复发生存率较好相关(P=0.012)。进一步的组织微阵列结果表明,TMEM176A 水平高的患者与淋巴结转移(P=0.045)和总体生存率较好相关(P=0.032)。在 Capan-1 和 PANC-1 细胞中过表达 TMEM176A 可抑制胰腺癌细胞的增殖、侵袭和迁移,并诱导细胞凋亡。TMEM176A 抑制了胰腺癌细胞中的 ERK 信号通路。

结论

TMEM176A 通过抑制 ERK 信号通路抑制胰腺癌细胞的生长和迁移。

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