GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence

GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence

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 a...

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Main Authors: Wensheng Chen, Zhipeng Chen, Miaomiao Zhang, Yahui Tian, Lu Liu, Ruirui Lan, Guandi Zeng, Xiaolong Fu, Guoqing Ru, Wanting Liu, Liang Chen, Zhenzhen Fan
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-06-01
Series:Frontiers in Oncology
Subjects:
lung cancer
tumor suppressor genes
GATA6
p21
AKT
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2020.00824/full
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spelling doaj-f519d2b90c874532b3f4d6b2d078001f2020-11-25T03:29:38ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-06-011010.3389/fonc.2020.00824516270GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell SenescenceWensheng Chen0Zhipeng Chen1Miaomiao Zhang2Yahui Tian3Lu Liu4Ruirui Lan5Guandi Zeng6Xiaolong Fu7Guoqing Ru8Wanting Liu9Liang Chen10Zhenzhen Fan11Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaInternational Department, The Affiliated High School of SCNU, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaDepartment of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, ChinaLung 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.https://www.frontiersin.org/article/10.3389/fonc.2020.00824/fulllung cancertumor suppressor genesGATA6p21AKT
collection DOAJ
language English
format Article
sources DOAJ
author Wensheng Chen
Zhipeng Chen
Miaomiao Zhang
Yahui Tian
Lu Liu
Ruirui Lan
Guandi Zeng
Xiaolong Fu
Guoqing Ru
Wanting Liu
Liang Chen
Zhenzhen Fan
spellingShingle Wensheng Chen
Zhipeng Chen
Miaomiao Zhang
Yahui Tian
Lu Liu
Ruirui Lan
Guandi Zeng
Xiaolong Fu
Guoqing Ru
Wanting Liu
Liang Chen
Zhenzhen Fan
GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence
Frontiers in Oncology
lung cancer
tumor suppressor genes
GATA6
p21
AKT
author_facet Wensheng Chen
Zhipeng Chen
Miaomiao Zhang
Yahui Tian
Lu Liu
Ruirui Lan
Guandi Zeng
Xiaolong Fu
Guoqing Ru
Wanting Liu
Liang Chen
Zhenzhen Fan
author_sort Wensheng Chen
title GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence
title_short GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence
title_full GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence
title_fullStr GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence
title_full_unstemmed GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence
title_sort gata6 exerts potent lung cancer suppressive function by inducing cell senescence
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2020-06-01
description 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.
topic lung cancer
tumor suppressor genes
GATA6
p21
AKT
url https://www.frontiersin.org/article/10.3389/fonc.2020.00824/full
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