Huang Chuanqian, Chen Renli, Zheng Fangjing, Tang Yirong, Wang Xiukang, Chen Zichun, Lai Xiaolan
Department of Medical Oncology and Radiotherapy, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, 352000, Fujian, China.
Department of Hematology and Rheumatism, Ningde Municipal Hospital Affiliated to Ningde Normal University, Ningde, 352000, Fujian, China.
Cancer Cell Int. 2021 Feb 19;21(1):127. doi: 10.1186/s12935-021-01828-9.
Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer related mortality worldwide. The 5-year survival rate is rather low owing to advanced unresectable and distant metastasis. The EMT has been widely implicated in the stemness, metastatic dormancy, and chemoresistance of different solid tumors. Given the fact that activating transcription factor-3 (ATF3) is a member of the ATF/CREB family of transcription factors and its role in regulation of GC recurrence and metastasis remain poorly understood, the aim of the present study was to investigate its potential impact in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties and GC aggression.
To elucidate the potential role of ATF3 in gastric cancer, we utilized SGC-7901 and MGC-803 gastric cancer cell lines as research models and constructed stable cell lines overexpressing ATF3. We conducted a series of assays including cell proliferation, colony formation, cell migration, tumorsphere formation, and invasion to investigate the functional roles of ATF3 in stemness of gastric cancer. The possible effect of ATF3 on epithelial-mesenchymal transition (EMT) was assessed through flow cytometry and qRT-PCR. In vivo functional effect of upregulation of ATF3 on tumor growth was examined in a mouse xenograft model.
We found that overexpression of ATF3 inhibited cell proliferation, colony formation, cell migration and invasion. In addition, up-regulation of ATF3 attenuated tumorsphere formation, cell stemness, and potentially decreased expression of EMT markers. Moreover, ATF3 overexpression inhibited tumorigenesis in mouse xenograft model.
Our data suggest a suppressive role of ATF3 in gastric cancer development. Our findings will provide a potential therapeutic strategy and novel drug target for gastric cancer.
胃癌（GC）是最常见的癌症之一，也是全球癌症相关死亡的第三大主要原因。由于晚期不可切除和远处转移，5年生存率相当低。上皮-间质转化（EMT）与不同实体瘤的干性、转移休眠和化疗耐药密切相关。鉴于激活转录因子3（ATF3）是转录因子ATF/CREB家族的成员，而其在胃癌复发和转移调控中的作用仍知之甚少，本研究旨在探讨其对上皮-间质转化（EMT）、癌症干细胞（CSC）特性及胃癌侵袭的潜在影响。
为阐明ATF3在胃癌中的潜在作用，我们利用SGC-7901和MGC-803胃癌细胞系作为研究模型，并构建了过表达ATF3的稳定细胞系。我们进行了一系列实验，包括细胞增殖、集落形成、细胞迁移、肿瘤球形成和侵袭实验，以研究ATF3在胃癌干性中的功能作用。通过流式细胞术和qRT-PCR评估ATF3对上皮-间质转化（EMT）的可能影响。在小鼠异种移植模型中检测上调ATF3对肿瘤生长的体内功能影响。
我们发现ATF3过表达抑制细胞增殖、集落形成、细胞迁移和侵袭。此外，ATF3上调减弱了肿瘤球形成、细胞干性，并可能降低EMT标志物的表达。此外，ATF3过表达抑制了小鼠异种移植模型中的肿瘤发生。
我们的数据表明ATF3在胃癌发展中起抑制作用。我们的研究结果将为胃癌提供一种潜在的治疗策略和新的药物靶点。
