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DMBT1通过靶向PTEN,经由PI3K/AKT信号通路抑制胆囊癌进展。

DMBT1 suppresses progression of gallbladder carcinoma through PI3K/AKT signaling pathway by targeting PTEN.

作者信息

Sheng Shen, Jiwen Wang, Dexiang Zhang, Bohao Zheng, Yueqi Wang, Han Liu, Xiaoling Ni, Tao Suo, Liu Houbao

机构信息

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of General Surgery, Zhongshan-Xuhui Hospital Affiated to Fudan University, Shanghai, China.

出版信息

Biosci Biotechnol Biochem. 2019 Dec;83(12):2257-2264. doi: 10.1080/09168451.2019.1654361. Epub 2019 Aug 14.

Abstract

Gallbladder carcinoma (GBC) is a highly lethal malignancy of the gastrointestinal tract. Despite extensive research, the underlying molecular mechanism of GBC remains largely unclear. Deleted in malignant brain tumors 1 (DMBT1) is low-expression during cancer progression and as a potential tumor-suppressor gene in various types of cancer. However, its role in Gallbladder cancer remains poorly understood. Here, we found that DMBT1 was significantly low-expression and deletion of copy number in GBC tissues by qRT-PCR and Western blot. Overexpression of DMBT1 impaired survival, promoted apoptosis in GBC cells , and inhibited tumor progression . Further study of underlying mechanisms demonstrated that DMBT1 combined with PTEN which could stabilize PTEN protein, resulting in inhibiting the activation of PI3K/AKT signaling pathway. Our study revealed a new sight of DMBT1 as a tumor-suppressor gene on the PI3K/AKT pathway in GBC, which may be a potential therapeutic target for improving treatment.

摘要

胆囊癌(GBC)是一种胃肠道高致死性恶性肿瘤。尽管进行了广泛研究,但GBC的潜在分子机制仍不清楚。恶性脑肿瘤缺失基因1(DMBT1)在癌症进展过程中低表达,是多种癌症中潜在的肿瘤抑制基因。然而,其在胆囊癌中的作用仍知之甚少。在此,我们通过qRT-PCR和蛋白质免疫印迹法发现,DMBT1在GBC组织中显著低表达且存在拷贝数缺失。DMBT1过表达损害了GBC细胞的生存能力,促进其凋亡,并抑制肿瘤进展。对潜在机制的进一步研究表明,DMBT1与PTEN结合,可稳定PTEN蛋白,从而抑制PI3K/AKT信号通路的激活。我们的研究揭示了DMBT1作为GBC中PI3K/AKT途径上的肿瘤抑制基因的新视角,这可能是改善治疗的潜在靶点。

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