GATA-6 transcriptionally inhibits Shh to repress cell proliferation and migration in lung squamous cell carcinoma. (October 2019)

• Record Type: Journal Article
• Authors: Xu, Linlin; Deng, Suyue; Xiong, Huanting; Shi, Wei; Luo, Shiwen; Chen, Limin
• Is Part Of: International journal of biochemistry & cell biology. Volume 115(2019)
• Publication Date: 2019-10
• Subjects: GATA-6 -- Sonic hedgehog (Shh) -- Lung squamous carcinoma (LSCC) -- Proliferation -- Migration; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2019.105591
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: GATA-6 is downregulated in LSCC. GATA-6 inhibits cell proliferation and migration of LSCC cells. GATA-6 transcriptionally represses Shh expression in LSCC. Shh rescues GATA-6-induced inhibition of LSCC cell proliferation and migration. Abstract: GATA-6 is a transcription factor that participates in cell lineage differentiation and organogenesis in many tissue types. The abnormal expression of GATA-6 is associated with the development of diverse cancers. GATA-6 acts as an oncogene or tumor suppressor based on tumor origin. Here, we investigated the effects of GATA-6 on lung squamous cell carcinoma (LSCC). We found that GATA-6 was significantly reduced in LSCC tissues compared with the paired normal tissues. The overexpression of GATA-6 inhibited LSCC cell proliferation and migration. Importantly, a luciferase reporter assay and chromatin immunoprecipitation assay demonstrated that GATA-6 negatively regulated the expression of sonic hedgehog (Shh) by directly binding to its promoter region. Furthermore, N-Shh stimulation rescued the inhibition of LSCC cell proliferation and migration upon GATA-6 overexpression. Thus, GATA-6 inhibited the proliferation and migration of LSCC cells by transcriptionally inhibiting the expression of Shh, indicating that targeting GATA-6 may be a potential approach for LSCC therapy.