GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence

Wensheng Chen; Zhipeng Chen; Miaomiao Zhang; Yahui Tian; Lu Liu; Ruirui Lan; Guandi Zeng; Xiaolong Fu; Guoqing Ru; Wanting Liu; Liang Chen; Zhenzhen Fan

doi:10.3389/fonc.2020.00824

GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence

Front Oncol. 2020 Jun 12:10:824. doi: 10.3389/fonc.2020.00824. eCollection 2020.

Authors

Affiliations

¹ Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
² International Department, The Affiliated High School of SCNU, Guangzhou, China.
³ Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
⁴ Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes (TSGs) play a critical role in restricting tumorigenesis and impact the therapeutic effect of various treatments. However, TSGs remain to be systemically determined in lung cancer. Here, we identified GATA6 as a potent lung cancer TSG. GATA6 inhibited lung cancer cell growth in vitro and tumorigenesis in vivo. Mechanistically, GATA6 upregulated p53 and p21 mRNA while it inhibited AKT activation to stabilize p21 protein, thus inducing lung cancer cell senescence. Furthermore, we showed that ectopic expression of GATA6 led to dramatic slowdown of growth rate of established lung tumor xenograft in vivo.

Keywords: AKT; GATA6; lung cancer; p21; tumor suppressor genes.