PMID- 31442607 OWN - NLM STAT- MEDLINE DCOM- 20200420 LR - 20200420 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 115 DP - 2019 Oct TI - GATA-6 transcriptionally inhibits Shh to repress cell proliferation and migration in lung squamous cell carcinoma. PG - 105591 LID - S1357-2725(19)30168-2 [pii] LID - 10.1016/j.biocel.2019.105591 [doi] AB - 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. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Xu, Linlin AU - Xu L AD - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China. FAU - Deng, Suyue AU - Deng S AD - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China. FAU - Xiong, Huanting AU - Xiong H AD - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China. FAU - Shi, Wei AU - Shi W AD - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; School of Pharmacy, Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China. FAU - Luo, Shiwen AU - Luo S AD - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China. FAU - Chen, Limin AU - Chen L AD - Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi 330006, China. Electronic address: liminchen@ncu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190820 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (GATA6 Transcription Factor) RN - 0 (Hedgehog Proteins) RN - 0 (SHH protein, human) SB - IM MH - Carcinoma, Squamous Cell/*pathology MH - *Cell Movement MH - Cell Proliferation MH - GATA6 Transcription Factor/*metabolism MH - Gene Expression Regulation, Neoplastic MH - HEK293 Cells MH - Hedgehog Proteins/*genetics MH - Humans MH - Lung Neoplasms/*pathology MH - *Transcription, Genetic OTO - NOTNLM OT - GATA-6 OT - Lung squamous carcinoma (LSCC) OT - Migration OT - Proliferation OT - Sonic hedgehog (Shh) EDAT- 2019/08/24 06:00 MHDA- 2020/04/21 06:00 CRDT- 2019/08/24 06:00 PHST- 2019/04/16 00:00 [received] PHST- 2019/07/19 00:00 [revised] PHST- 2019/08/19 00:00 [accepted] PHST- 2019/08/24 06:00 [pubmed] PHST- 2020/04/21 06:00 [medline] PHST- 2019/08/24 06:00 [entrez] AID - S1357-2725(19)30168-2 [pii] AID - 10.1016/j.biocel.2019.105591 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2019 Oct;115:105591. doi: 10.1016/j.biocel.2019.105591. Epub 2019 Aug 20.