SALL4 promotes the tumorigenicity of cervical cancer cells through activation of Wnt/β-catenin pathway via CTNNB1

SALL4 is overexpressed in many cancers and is found to be involved in tumorigenesis and tumor progression. However, the function of SALL4 in cervical cancer remains unknown. Here, we showed that the expression of SALL4 was gradually increased from normal cervical tissue (NC) to high-grade squamous intraepithelial lesions (HSIL) and then to squamous cervical carcinoma (SCC). SALL4 was up-regulated or down-regulated in cervical cancer cells by stably transfecting a SALL4-expressing plasmid or a shRNA plasmid targeting SALL4, respectively. In vitro, cell growth curves and MTT assays showed that SALL4 promoted the cell proliferation of cervical cancer cells. In vivo, xenograft experiments verified that SALL4 enhanced the tumor formation of cervical cancer cells in female BALB/c nude mice. Cell cycle analysis by FACS found that SALL4 accelerates the cell cycle transition from the G0/G1 phase to the S phase. TOP/FOP-Flash reporter assay revealed that SALL4 significantly up-regulates the activity of Wnt/β-catenin pathway. Western blotting showed that the expression of β-catenin and important downstream genes, including c-Myc and cyclin D1, were increased by SALL4 in cervical cancer cells. Furthermore, the dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays confirmed that SALL4 transcriptionally activated CTNNB1 by physically interacting with its promoters. Taken together, The results of this study demonstrated that SALL4 may promote cell proliferation and tumor formation of cervical cancer cells by up-regulating the activity of the Wnt/β-catenin signaling pathway by directly binding to the CTNNB1 promoter and trans-activating CTNNB1. This article is protected by copyright. All rights reserved.