Zhang Fang, Jiang Zheng
Department of Gastroenterology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Onco Targets Ther. 2020 Apr 24;13:3489-3500. doi: 10.2147/OTT.S242386. eCollection 2020.
Odd-skipped related transcription factor 1 (OSR1) is a newly identified tumor suppressor in many tumor types. However, the role and mechanism of OSR1 in colon adenocarcinoma (COAD) remain unknown.
OSR1 expression was detected in COAD tissues and cells. COAD cells with OSR1 overexpression or knockdown were analyzed by in vitro CCK-8, transwell and flow cytometry assays, and by in vivo xenograft model.
OSR1 expression was downregulated in COAD and low expression level of OSR1 was positively correlated with tumor stage and lymph node metastasis. Furthermore, low OSR1 expression was significantly associated with poor overall survival (OS) and distant metastasis-free survival (DMFS). Lentivirus-mediated restoration of OSR1 expression-inhibited proliferation, invasion and migration while induced cell cycle arrest and apoptosis in COAD cells in vitro, and inhibited tumor growth in vivo. In contrast, OSR1 knockdown promoted proliferation, invasion and migration in COAD cells in vitro. Mechanistically, OSR1 exerted anticancer effects by inhibiting FAK-mediated activation of Akt and MAPK pathways.
Our findings suggest that OSR1 functions as a tumor suppressor in COAD by suppressing FAK-mediated activation of Akt and MAPK pathways.
奇跳相关转录因子1（OSR1）是在多种肿瘤类型中新发现的肿瘤抑制因子。然而，OSR1在结肠腺癌（COAD）中的作用和机制仍不清楚。
检测COAD组织和细胞中OSR1的表达。通过体外CCK-8、Transwell和流式细胞术分析以及体内异种移植模型，对过表达或敲低OSR1的COAD细胞进行分析。
COAD中OSR1表达下调，OSR1低表达水平与肿瘤分期和淋巴结转移呈正相关。此外，OSR1低表达与总生存期（OS）和无远处转移生存期（DMFS）差显著相关。慢病毒介导的OSR1表达恢复在体外抑制COAD细胞的增殖、侵袭和迁移，同时诱导细胞周期停滞和凋亡，并在体内抑制肿瘤生长。相反，敲低OSR1可促进COAD细胞在体外的增殖、侵袭和迁移。机制上，OSR1通过抑制FAK介导的Akt和MAPK通路激活发挥抗癌作用。
我们的研究结果表明，OSR1通过抑制FAK介导的Akt和MAPK通路激活在COAD中发挥肿瘤抑制作用。
