title: Inhibition of SALL4 reduces tumorigenicity involving epithelial-mesenchymal transition via Wnt/β-catenin pathway in esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Yue
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Qin
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Chaoqi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago, IL60611, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Yu
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. yizhang@zzu.edu.cn.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. yizhang@zzu.edu.cn.|School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. yizhang@zzu.edu.cn.|Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan, 450052, China. yizhang@zzu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: C472575:SALL4 protein, human; D014157:Transcription Factors
keywords: Epithelial-mesenchymal transition (EMT); Esophageal squamous cell carcinoma (ESCC); Prognostic marker; SALL4; Stemness