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.
Highlights
Lung cancer is the leading cause of cancer-related deaths globally [1,2,3]
We checked GATA6 expression level in lung cancer cell lines commonly used in cancer research community through quantitative reverse transcription PCR, including four pairs of lung adenocarcinoma/para-tumoral tissues as references for GATA6 expression in tumoral and normal lung tissues
We found that GATA6 was a clinically relevant tumor suppressor genes (TSGs) in lung cancer
Summary
Lung cancer is the leading cause of cancer-related deaths globally [1,2,3]. Chemotherapy, targeting therapy, and immunotherapy are mainstream treatment options for lung cancer patients in clinic [4, 5]. Despite the advances in multimodal therapies, the prognosis for lung cancer patients remains disappointingly dismal, with overall 5-year survival rate of only around 17% [6]. Gain-of-function mutations in driver oncogenes and loss-of-function mutations in tumor suppressor genes (TSGs) are thought to coordinately drive transformation of lung epithelial cells into tumorigenic cells. Driver oncogenes are relatively well-studied, with multiple targeting drugs available for lung cancer patients in clinic. TSGs remain to be systemically determined in lung cancer [7, 8]
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