Abstract
Pituitary tumor-transforming gene-1 (PTTG1) could acquire its metastasis-promoting effects via inducing epithelial-mesenchymal transition (EMT). However, its role and mechanism in EMT in esophageal squamous cell cancer (ESCC) had not been clearly elucidated. Here, we demonstrated that PTTG1 was overexpressed in ESCC cell lines and tissues especially those with lymph node metastasis. Down regulation of PTTG1 levels dampened the ESCC cells invasion, migration, proliferation ability and colony formation in vitro and inhibited the growth of mouse xenograft model of ESCC cells in vivo. In addition, our in vitro and in vivo experiments consistently showed that decreased PTTG1 led to the inhibition of EMT process. Glioma-associated oncogene homolog1 (GLI1), a key factor in HH-GLI signaling pathway, was also overexpressed in ESCC cells and tissues. Mechanistic studies demonstrated that decreased PTTG1 mitigated the expression levels of GLI1 in vitro and in vivo and ChIP assay also indicated that PTTG1 cooperated with GLI1 by binding to its promoter. Furthermore, overexpression of GLI1 rescued the EMT inhibited by down regulation of PTTG1 in vitro. Together, these data suggested that PTTG1 promoted the invasion ability of ESCC cells via EMT, more important, PTTG1 participated in EMT via activating the expression of GLI1 in ESCC. PTTG1 could be a candidate biomarker for defining ESCC metastasis and useful target for therapy.
Highlights
Esophageal squamous cell cancer (ESCC) is one of the most malignant diseases in China, causing more than 400000 deaths per year [1,2]
In order to further explore the role of Pituitary tumor-transforming gene-1 (PTTG1) and Glioma-associated oncogene homolog1 (GLI1) in the invasion and metastasis of esophageal squamous cell cancer (ESCC), we detected the expression levels of PTTG1 and GLI1 in three ESCC cell lines with different metastasis ability and immortalized human esophageal epithelial cell line SHEE
We identified that PTTG1 acted as a promoter in inducing epithelial-mesenchymal transition (EMT) and cancer metastasis in ESCC via activating GLI1, an important factor of the HH-gliomaassociated oncogene homolog (GLI) signaling pathway
Summary
Esophageal squamous cell cancer (ESCC) is one of the most malignant diseases in China, causing more than 400000 deaths per year [1,2]. Great efforts have been made to improve the treatment of patients with ESCC, the 5-year-survival rate is low for those with invasion and metastasis [3]. It is urgent for us to achieve timelier and earlier-stage diagnosis. Epithelial-mesenchymal transition (EMT), originally a normal cell differentiation process during early development, has been described in invasion and metastasis in certain cancers [4,5,6]. EMT can be awoken and make the cancer cells lose their epithelial phenotype, obtain mesenchymal phenotype and acquire metastasis ability in the end [6]. Switch on EMT in cancer cells is induced by many different signaling pathways after these pathways are activated by various stimuli [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
