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SYNPO2通过调节YAP-KLF5轴抑制缺氧诱导的结肠癌细胞增殖和迁移。

SYNPO2 suppresses hypoxia-induced proliferation and migration of colorectal cancer cells by regulating YAP-KLF5 axis.

作者信息

OuYang Canhui, Xie Yun, Fu Qubo, Xu Guofeng

机构信息

Department of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China.

Department of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, China.

出版信息

Tissue Cell. 2021 Dec;73:101598. doi: 10.1016/j.tice.2021.101598. Epub 2021 Jul 26.

Abstract

Colorectal cancer (CRC) is one of the most common tumors that has a high incidence worldwide. Targeted therapy for CRC has received much attention recently. It is still necessary to develop novel and promising therapeutic targets to improve the prognosis. SYNPO2, also known as synapsopoprotein 2 or myopod, encodes actin binding proteins and has been characterized as a tumor suppressor for aggressive cancers. SYNPO2 has been reported to inhibit the activity of YAP/TAZ. However, whether SYNPO2 could regulate the progression of CRC through the YAP/YAZ signaling pathway remains unclear. Herein, it was found that the expression of SYNPO2 was low in hypoxia-exposed CRC cells, consistent with the data from TCGA database. SYNPO2 inhibited the growth of CRC cells upon hypoxia treatment and promoted the cell apoptosis. Additionally, SYNPO2 inhibited the migration and epithelial-mesenchymal transformation (EMT) CRC cell upon hypoxia treatment. Mechanically, the results demonstrated that SYNPO2 suppressed hypoxia-induced progression of CRC by regulating YAP-Kruppel like factor 5 (KLF5) axis. Therefore, SYNPO2 can serve as a promising therapeutic target for CRC treatment.

摘要

结直肠癌(CRC)是全球发病率较高的常见肿瘤之一。近年来,CRC的靶向治疗备受关注。开发新的、有前景的治疗靶点以改善预后仍然很有必要。SYNPO2,也称为突触素蛋白2或肌足蛋白,编码肌动蛋白结合蛋白,已被确定为侵袭性癌症的肿瘤抑制因子。据报道,SYNPO2可抑制YAP/TAZ的活性。然而,SYNPO2是否能通过YAP/YAZ信号通路调节CRC的进展仍不清楚。在此研究中,发现缺氧处理的CRC细胞中SYNPO2表达较低,这与TCGA数据库的数据一致。缺氧处理后,SYNPO2抑制CRC细胞的生长并促进细胞凋亡。此外,缺氧处理后,SYNPO2抑制CRC细胞的迁移和上皮-间质转化(EMT)。机制上,结果表明SYNPO2通过调节YAP-克鲁ppel样因子5(KLF5)轴抑制缺氧诱导的CRC进展。因此,SYNPO2可作为CRC治疗的一个有前景的治疗靶点。

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