Obesity Suppresses Cell-Competition-Mediated Apical Elimination of RasV12-Transformed Cells from Epithelial Tissues.

Obesity Suppresses Cell-Competition-Mediated Apical Elimination of RasV12-Transformed Cells from Epithelial Tissues.
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DOI:
10.1016/j.celrep.2018.03.104
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发表时间:
2018-04-24
期刊:
影响因子:
8.8
通讯作者:
Fujita Y
Fujita Y
中科院分区:
生物学1区
文献类型:
--
作者:
Sasaki A;Nagatake T;Egami R;Gu G;Takigawa I;Ikeda W;Nakatani T;Kunisawa J;Fujita Y

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最近的研究表明,新出现的转化细胞通常通过与周围正常上皮细胞的细胞竞争而从上皮组织中消除。这种癌症预防现象被称为上皮细胞抗癌防御(EDAC)。然而,在很大程度上仍然不清楚EDAC是否以及如何在致癌过程中减少。在这项研究中,使用细胞竞争小鼠模型,我们表明高脂饮食(HFD)喂养大大减弱了RasV12转化细胞从肠和胰腺上皮中顶端消除的频率。这个过程涉及脂质代谢和慢性炎症。此外,阿司匹林治疗显著促进了HFD喂养小鼠上皮组织中转化细胞的根除。因此,我们的工作表明,肥胖可以深刻影响正常细胞和转化细胞之间的竞争相互作用,为细胞竞争和癌症预防医学提供见解。Sasaki等人使用细胞竞争小鼠模型证明,高脂肪饮食喂养显著减弱了从肠和胰腺上皮细胞中顶端消除RasV12转化细胞的频率。这些结果表明,肥胖可以深刻地影响正常细胞和转化细胞之间的竞争相互作用在癌变的初始阶段。
Recent studies have revealed that newly emerging transformed cells are often eliminated from epithelial tissues via cell competition with the surrounding normal epithelial cells. This cancer preventive phenomenon is termed epithelial defense against cancer (EDAC). However, it remains largely unknown whether and how EDAC is diminished during carcinogenesis. In this study, using a cell competition mouse model, we show that high-fat diet (HFD) feeding substantially attenuates the frequency of apical elimination of RasV12-transformed cells from intestinal and pancreatic epithelia. This process involves both lipid metabolism and chronic inflammation. Furthermore, aspirin treatment significantly facilitates eradication of transformed cells from the epithelial tissues in HFD-fed mice. Thus, our work demonstrates that obesity can profoundly influence competitive interaction between normal and transformed cells, providing insights into cell competition and cancer preventive medicine. Sasaki et al. demonstrate using a cell competition mouse model that high-fat diet feeding substantially attenuates the frequency of apical elimination of RasV12-transformed cells from intestinal and pancreatic epithelia. These results indicate that obesity can profoundly influence competitive interaction between normal and transformed cells at the initial stage of carcinogenesis.
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