Intestinal epithelial cell autophagy deficiency suppresses inflammation-associated colon tumorigenesis.
Intestinal epithelial cell autophagy deficiency suppresses inflammation-associated colon tumorigenesis.
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肠上皮细胞自噬缺陷抑制炎症相关的结肠肿瘤发生
DOI：
10.1016/j.omtn.2022.02.012
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发表时间：
2022-06-14
期刊：
影响因子：
--
通讯作者：
Han W
中科院分区：
文献类型：
--
作者：
Liu H;Lou J;Liu Y;Liu Z;Xie J;Sun J;Pan H;Han W
结肠炎相关癌（CAC）与慢性炎症密切相关，但其分子机制尚未得到全面阐述。在本研究中，对自噬在氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的结肠肿瘤（人类CAC的小鼠模型）的起始和进展中的作用进行了研究。肠上皮细胞（IEC）特异性缺失自噬相关基因7（Atg 7）的小鼠在肿瘤数量、负荷和高度异型增生风险方面显着降低。肠上皮细胞自噬缺陷导致T细胞，特别是CD 8 + T淋巴细胞在结肠固有层中的积聚。此外，研究发现自噬通过维持上皮屏障功能和促进IEC的存活和增殖来保护DSS诱导的肠损伤。从机制上讲，自噬在肠上皮细胞中增强了上皮细胞STAT 3/ERK的激活，从而促进了CAC发生过程中结肠上皮细胞的存活和增殖。因此，这些发现揭示了自噬在激活结肠保护，再生和肿瘤发生过程中的重要作用。自噬对于维持细胞存活和稳态至关重要。使用IEC特异性Atg 7敲除小鼠，Liu et al.证明在CAC的发展过程中，IEC中的自噬维持屏障完整性并增强上皮STAT 3/ERK的活化以促进结肠上皮细胞的存活和增殖
Colitis-associated cancer (CAC) is closely related to chronic inflammation, whose underlying molecular mechanism, however, has not been elaborated comprehensively. In the current study, an investigation was conducted on the role of autophagy in the initiation and progression of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon tumors, a mouse model for CAC in humans. Mice with the intestinal epithelial cell (IEC)-specific deletion of the autophagy-related gene 7 (Atg7) saw a significant decrease in tumor number, burden, and risk of high-grade dysplasia. The autophagy deficiency of IECs resulted in the accumulation of T cells, especially CD8+ T lymphocytes in colon lamina propria. Furthermore, it was found that autophagy protects against DSS-induced intestinal injury through maintaining epithelial barrier function and promoting the survival and proliferation of IECs. Mechanistically, autophagy in IECs enhanced the activation of epithelial STAT3/ERK to promote the survival and proliferation of colonic epithelial cells during the development of CAC. Therefore, the findings unveil the essential role of autophagy in activating the processes of colonic protection, regeneration, and tumorigenesis. Autophagy is critical for the maintenance of cell survival and homeostasis. Using IEC-specific Atg7 knockout mice, Liu et al. demonstrate that autophagy in IECs maintains barrier integrity and enhances the activation of epithelial STAT3/ERK to promote the survival and proliferation of colonic epithelial cells during the development of CAC
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影响因子：
3.1
作者：
Chen, Zhihong;Li, Yanchun;Zhang, Chi;Yi, Hongmei;Wu, Chang;Wang, Junpu;Liu, Yuwu;Tan, Jieqiong;Wen, Jifang
通讯作者：
Wen, Jifang
影响因子：
3.7
作者：
Jo YK;Kim SC;Park IJ;Park SJ;Jin DH;Hong SW;Cho DH;Kim JC
通讯作者：
Kim JC
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T
影响因子：
64.5
作者：
Cadwell K;Patel KK;Maloney NS;Liu TC;Ng AC;Storer CE;Head RD;Xavier R;Stappenbeck TS;Virgin HW
通讯作者：
Virgin HW