GATA-6 transcriptionally inhibits Shh to repress cell proliferation and migration in lung squamous cell carcinoma.
GATA-6 transcriptionally inhibits Shh to repress cell proliferation and migration in lung squamous cell carcinoma.
复制标题
GATA-6 转录抑制 Shh，从而抑制肺鳞状细胞癌中的细胞增殖和迁移。
DOI：
10.1016/j.biocel.2019.105591
复制
发表时间：
2019-10
期刊：
影响因子：
--
通讯作者：
Chen Limin
中科院分区：
文献类型：
--
作者：
Xu Linlin;Deng Suyue;Xiong Huanting;Shi Wei;Luo Shiwen;Chen Limin
GATA-6是一种转录因子，参与多种组织的细胞系分化和器官发生。GATA-6的异常表达与多种肿瘤的发生发展有关。根据肿瘤来源，GATA-6起癌基因或肿瘤抑制因子的作用。在这里，我们研究了GATA-6对肺鳞状细胞癌(LSCC)的作用。我们发现，与配对的正常组织相比，喉鳞癌组织中GATA-6的表达显著降低。GATA-6过表达抑制了LSCC细胞的增殖和迁移。重要的是，荧光素酶报告实验和染色质免疫沉淀实验表明，GATA-6通过直接与Sonic Hedgehog(Shh)启动子区域结合来负调控Sonic Hedgehog(Shh)的表达。此外，N-Shh刺激挽救了对GATA-6过表达抑制LSCC细胞增殖和迁移的作用。因此，GATA-6通过转录抑制Shh的表达来抑制LSCC细胞的增殖和迁移，提示靶向GATA-6可能是一种潜在的LSCC治疗方法。
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.
登录
查看更多内容
影响因子：
11.8
作者：
Zhang, Zhen;Verheyden, Jamie M.;Hassell, John A.;Sun, Xin
通讯作者：
Sun, Xin
影响因子：
14.8
作者：
Stanton, Benjamin Z.;Peng, Lee F.;Maloof, Nicole;Nakai, Kazuo;Wang, Xiang;Duffner, Jay L.;Taveras, Kennedy M.;Hyman, Joel M.;Lee, Sam W.;Koehler, Angela N.;Chen, James K.;Fox, Julia L.;Mandinova, Anna;Schreiber, Stuart L.
通讯作者：
Schreiber, Stuart L.
影响因子：
3.7
作者：
Zhong Y;Wang Z;Fu B;Pan F;Yachida S;Dhara M;Albesiano E;Li L;Naito Y;Vilardell F;Cummings C;Martinelli P;Li A;Yonescu R;Ma Q;Griffin CA;Real FX;Iacobuzio-Donahue CA
通讯作者：
Iacobuzio-Donahue CA
影响因子：
3.1
作者：
Yunqi H;Fangrui Y;Yongyan Y;Yunjian J;Wenhui Z;Kun C;Min L;Xianfeng L;Caixia B
通讯作者：
Caixia B
GATA6通过调节miR-520b/CREB1轴抑制胃癌迁移和转移
影响因子：
9
作者：
Liu, Hao;Du, Feng;Zhao, Xiaodi
通讯作者：
Zhao, Xiaodi