Inhibition of SALL4 reduces tumorigenicity involving epithelial-mesenchymal transition via Wnt/β-catenin pathway in esophageal squamous cell carcinoma.
Inhibition of SALL4 reduces tumorigenicity involving epithelial-mesenchymal transition via Wnt/β-catenin pathway in esophageal squamous cell carcinoma.
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DOI：
10.1186/s13046-016-0378-z
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发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
He J;Zhou M;Chen X;Yue D;Yang L;Qin G;Zhang Z;Gao Q;Wang D;Zhang C;Huang L;Wang L;Zhang B;Yu J;Zhang Y
越来越多的证据表明，SALL 4在肿瘤进展和转移中起着至关重要的作用。然而，SALL 4促进食管鳞状细胞癌（ESCC）的分子机制仍有待阐明。采用实时荧光定量PCR、免疫组化和蛋白质印迹法检测基因和蛋白质表达谱。小发夹RNA用于评估SALL 4在细胞系和动物模型中的作用。CCK 8、流式细胞术和transwell-matrigel法检测细胞增殖、凋亡和侵袭能力。球体形成测定用于癌症干细胞衍生和表征。我们的研究表明，转录因子SALL 4在大多数人食管鳞癌组织中过表达，并与预后不良密切相关。我们在TE 7和EC 109细胞中建立了使用短发夹RNA敲减SALL 4的慢病毒系统。沉默SALL 4基因可抑制细胞增殖，诱导细胞凋亡，使细胞周期阻滞于G1期，降低细胞的迁移/侵袭能力，降低细胞克隆形成能力和干细胞性。此外，下调SALL 4表达可增强食管鳞癌细胞对顺铂的敏感性。异种移植肿瘤模型显示，沉默SALL 4降低了体内形成肿瘤的能力。此外，我们的研究表明，SALL 4通过Wnt/β-catenin信号通路调节ESCC细胞的干细胞性和上皮-间充质转化中发挥重要作用。我们的研究结果表明，SALL 4可能作为一个功能性的标志物，食管鳞癌干细胞，预后的一个重要标志物和食管鳞癌的靶向治疗的一个有吸引力的候选人。
Growing evidence suggests that SALL4 plays a vital role in tumor progression and metastasis. However, the molecular mechanism of SALL4 promoting esophageal squamous cell carcinoma (ESCC) remains to be elucidated. The gene and protein expression profiles- were examined by using quantitative real-time PCR, immunohistochemistry and western blotting. Small hairpin RNA was used to evaluate the role of SALL4 both in cell lines and in animal models. Cell proliferation, apoptosis and invasion were assessed by CCK8, flow cytometry and transwell-matrigel assays. Sphere formation assay was used for cancer stem cell derivation and characterization. Our study showed that the transcription factor SALL4 was overexpressed in a majority of human ESCC tissues and closely correlated with a poor outcome. We established the lentiviral system using short hairpin RNA to knockdown SALL4 in TE7 and EC109 cells. Silencing of SALL4 inhibited the cell proliferation, induced apoptosis and the G1 phase arrest in cell cycle, decreased the ability of migration/invasion, clonogenicity and stemness in vitro. Besides, down-regulation of SALL4 enhanced the ESCC cells’ sensitivity to cisplatin. Xenograft tumor models showed that silencing of SALL4 decreased the ability to form tumors in vivo. Furthermore, our study demonstrated that SALL4 played a vital role in modulating the stemness of ESCC cells via Wnt/β-catenin signaling pathway and in epithelial-mesenchymal transition. Our results revealed that SALL4 might serve as a functional marker for ESCC cancer stem cell, a crucial marker for prognosis and an attractive candidate for target therapy of ESCC.