title: Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma.
abstract: Cancer stem cells (CSCs) are defined as a rare subpopulation of undifferentiated cells with biological characteristics that include the capacity for self-renewal, differentiation into various lineages, and tumor initiation. To explore the mechanism of CSCs in esophageal squamous cell carcinoma (ESCC), we focused on Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a target gene of the Wnt signaling pathway, which has been identified as a marker of intestinal stem cells and shown to be overexpressed in several human malignancies. Lgr5 expression was significantly correlated with lymph node metastasis, increased depth of invasion, increased tumor size, advanced differentiation, higher AJCC stage and poorer survival. Silencing of Lgr5 expression in the ESCC cell line KYSE450 by small interfering RNA (siRNA) strongly inhibited cell proliferation, migration and invasion ability, the expression of CSCs-related genes and Wnt/β-catenin signaling. In addition, Lgr5 was highly expressed in ESCC spheroid body cells, which were identified by high expression of CSCs-related genes, and high tumorigenicity in vivo. Taken together, these results demonstrate that Lgr5 activation of Wnt/β-catenin signaling is a potential mechanism to promote the progression of ESCC and ESCC stem cell renewal, and Lgr5 may be used as a molecular target for the development of treatments for ESCC.
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Lv
authors.affiliation: University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Cincinnati, OH, USA.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Xiang Ya Hospital of Central South University, Hunan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Li
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xue-Liang
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xin-Ya
authors.initials: XY
authors.lastname: Gao
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xian-Fei
authors.initials: XF
authors.lastname: Ding
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Cai
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Liu-Xing
authors.initials: LX
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D060449:Wnt Signaling Pathway; D000098907:R-Spondins
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C116884:LGR5 protein, human; C557408:Rspo2 protein, human; D000098907:R-Spondins
keywords: Lgr5; cancer stem cells; esophageal squamous cell carcinoma; small interfering RNA; spheroid body cells