Hormonal Suppression of Stem Cells Inhibits Symmetric Cell Division and Gastric Tumorigenesis.,Cell Stem Cell

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Hormonal Suppression of Stem Cells Inhibits Symmetric Cell Division and Gastric Tumorigenesis.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.stem.2020.01.020
Wenju Chang ₁ , Hongshan Wang ₂ , Woosook Kim ₃ , Yang Liu ₄ , Huan Deng ₅ , Haibo Liu ₃ , Zhengyu Jiang ₃ , Zhengchuan Niu ₆ , Weiwei Sheng ₃ , Osmel Companioni Nápoles ₃ , Yihong Sun ₇ , Jianmin Xu ₈ , Antonia Sepulveda ₉ , Yoku Hayakawa ₁₀ , Adam J Bass ₄ , Timothy C Wang ₃

Affiliation

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Colorectal Cancer Center of Zhongshan Hospital, Fudan University, Shanghai 200032, China; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA; Gastric Cancer Center of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Division of Molecular and Cellular Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02138, USA.
Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA; The Fourth Affiliated Hospital of Nanchang University, Nanchang 330003, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Gastric Cancer Center of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Colorectal Cancer Center of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Cancer is believed to arise from stem cells, but mechanisms that limit the acquisition of mutations and tumor development have not been well defined. We show that a +4 stem cell (SC) in the gastric antrum, marked by expression of Cck2r (a GPCR) and Delta-like ligand 1 (DLL1), is a label-retaining cell that undergoes predominant asymmetric cell division. This +4 antral SC is Notch1low/ Numb+ and repressed by signaling from gastrin-expressing endocrine (G) cells. Chemical carcinogenesis of the stomach is associated with loss of G cells, increased symmetric stem cell division, glandular fission, and more rapid stem cell lineage tracing, a process that can be suppressed by exogenous gastrin treatment. This hormonal suppression is associated with a marked reduction in gastric cancer mutational load, as revealed by exomic sequencing. Taken together, our results show that gastric tumorigenesis is associated with increased symmetric cell division that facilitates mutation and is suppressed by GPCR signaling.

中文翻译：

干细胞的激素抑制抑制对称细胞分裂和胃肿瘤发生。

癌症被认为是由干细胞引起的，但限制突变获得和肿瘤发展的机制尚未明确定义。我们显示胃窦中的 +4 干细胞 (SC)，以 Cck2r（GPCR）和 Delta 样配体 1 (DLL1) 的表达为标志，是一种标记保留细胞，主要经历不对称细胞分裂。这个 +4 窦 SC 是 Notch1low/Numb+，并被来自表达胃泌素的内分泌 (G) 细胞的信号抑制。胃的化学致癌作用与 G 细胞丢失、对称干细胞分裂增加、腺体分裂和更快速的干细胞谱系追踪有关，这一过程可以通过外源性胃泌素治疗来抑制。正如外显子组测序所揭示的，这种激素抑制与胃癌突变负荷的显着降低有关。综合起来，

更新日期：2020-03-05

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