Downregulation of a putative tumor suppressor BMP4 by SOX2 promotes growth of lung squamous cell carcinoma

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Please use this identifier to cite or link to this item: https://ir.lib.ncu.edu.tw/handle/987654321/102530

Title:	Downregulation of a putative tumor suppressor BMP4 by SOX2 promotes growth of lung squamous cell carcinoma
Authors:	王陸海;Fang, Wen‐Tsen;Fan, Chi‐Chen;Li, Shih‐Miao;Jang, Te‐Hsuan;Lin, Hsiu‐Ping;Shih, Neng‐Yao;Chen, Chung‐Hsing;Wang, Tao‐Yeuen;Huang, Shiu‐Feng;Lee, Alan Yueh‐Luen;Liu, Ying‐Lan;Tsai, Fang‐Yu;Huang, Chih‐Ting;Yang, Su Jing;Yen, Lin‐Ju;Chuu, Chih‐Pin;Chen, Chih‐Yi;Hsiung, Chao A.;Chang, Jang‐Yang;Wang, Lu‐Hai;Chang, I‐Shou;Jiang, Shih Sheng
Contributors:	生醫理工學院生命科學系
Keywords:	Animals;Biological and medical sciences;BMP4;Bone Morphogenetic Protein 4 - metabolism;Cancer;Carcinoma, Non-Small-Cell Lung - genetics;Carcinoma, Non-Small-Cell Lung - metabolism;Carcinoma, Squamous Cell - genetics;Carcinoma, Squamous Cell - metabolism;Cell growth;Databases, Genetic;Down-Regulation;Gene expression;Gene Expression Profiling;Gene Expression Regulation, Neoplastic;Gene Silencing;Humans;Lung - metabolism;Lung cancer;Lung Neoplasms - genetics;Lung Neoplasms - metabolism;lung squamous cell carcinoma;Medical research;Medical sciences;Mice;Multiple tumors. Solid tumors. Tumors in childhood (general aspects);Neoplasm Transplantation;Oligonucleotide Array Sequence Analysis;Pneumology;Promoter Regions, Genetic;Protein expression;Signal Transduction;SOX2;SOXB1 Transcription Factors - metabolism;Stem cells;Tumors;Tumors of the respiratory system and mediastinum
Date:	2014-08-15
Issue Date:	2026-04-23 11:12:25 (UTC+8)
Publisher:	Wiley-Liss Inc.;Hoboken, NJ: Wiley-Blackwell
Abstract:	摘要： SOX2 is a transcription factor essential for self‐renewal and pluripotency of embryonic stem cells. Recently, SOX2 was found overexpressed in the majority of the lung squamous cell carcinoma (SQC), in which it acts as a lineage‐survival oncogene. However, downstream targets/pathways of SOX2 in lung SQC cells remain to be identified. Here, we show that BMP4 is a downstream target of SOX2 in lung SQC. We found that SOX2‐silencing‐mediated inhibition of cell growth was accompanied by upregulation of BMP4 mRNA and its protein expression. Meta‐analysis with 293 samples and qRT‐PCR validation with 73 clinical samples revealed an inversely correlated relationship between levels of SOX2 and BMP4 mRNA, and significantly lower mRNA levels in tumor than in adjacent normal tissues. This was corroborated by immunohistochemistry analysis of 35 lung SQC samples showing lower BMP4 protein expression in tumor tissues. Cell‐based experiments including siRNA transfection, growth assay and flow cytometry assay, further combined with a xenograft tumor model in mice, revealed that reactivation of BMP4 signaling could partially account for growth inhibition and cell cycle arrest in lung SQC cells upon silencing SOX2. Finally, chromatin immunoprecipitation analysis and luciferase reporter assay revealed that SOX2 could negatively regulate BMP4 promoter activity, possibly through binding to the promoter located in the first intron region of BMP4. Collectively, our findings suggest that BMP4 could act as a tumor suppressor and its downregulation by elevated SOX2 resulting in enhanced growth of lung SQC cells. What's new? The oncogene SOX2 is overexpressed in lung cancer. To find out how it contributes to cancer development, these authors investigated which genes were affected by silencing SOX2. They discovered that a lack of SOX2 significantly boosted the expression of the gene BMP4. As a member of the TGF‐β family, BMP4 seemed a good candidate for a key player in the cancer process. Further investigation revealed that tumor cells contain less BMP4, and that reactivation of BMP4 could slow tumor growth and halt cell proliferation. These findings may explain how SOX2 promotes tumor development. 其他題名： Int J Cancer 出版者： Hoboken, NJ: Wiley-Blackwell 出版日期： 2014-08-15 出處： International journal of cancer, 2014-08, Vol.135 (4), p.809-819 資源來源： Wiley Online Journals ** 版權： 2014 UICC 版權： 2015 INIST-CNRS 版權： 2014 UICC. 識別號： ISSN: 0020-7136 識別號： ISSN: 1097-0215 識別號： EISSN: 1097-0215 識別號： DOI: 10.1002/ijc.28734 識別號： PMID: 24477565 識別號： CODEN: IJCNAW
Appears in Collections:	[Department of Life Science] journal & Dissertation

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