Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer.
Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer.
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DOI：
10.1038/s41467-021-22450-3
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发表时间：
2021-04-16
影响因子：
16.6
通讯作者：
Nakano H
中科院分区：
文献类型：
--
作者：
Nishina T;Deguchi Y;Ohshima D;Takeda W;Ohtsuka M;Shichino S;Ueha S;Yamazaki S;Kawauchi M;Nakamura E;Nishiyama C;Kojima Y;Adachi-Akahane S;Hasegawa M;Nakayama M;Oshima M;Yagita H;Shibuya K;Mikami T;Inohara N;Matsushima K;Tada N;Nakano H
白细胞介素（IL）-11是细胞因子IL-6家族的成员，并且参与多种细胞应答，包括肿瘤发展。然而，IL-11产生细胞（IL-11+）的起源和功能尚未完全了解。为了在体内表征IL-11+细胞，我们产生了IL 11报告小鼠。IL-11+细胞出现在鼠肿瘤和急性结肠炎模型的结肠中。Il 11 ra 1或Il 11缺失减弱结肠炎相关结直肠癌的发展IL-11+细胞表达成纤维细胞标志物和与细胞增殖和组织修复相关的基因。IL-11通过STAT 3的磷酸化诱导结肠成纤维细胞和上皮细胞的活化。人类癌症数据库分析显示，IL-11+成纤维细胞中富集的基因表达在人类结直肠癌中升高，并与无复发生存率降低相关。IL-11+成纤维细胞通过分泌IL-11激活肿瘤细胞和成纤维细胞，从而在肿瘤微环境中构成肿瘤细胞和成纤维细胞之间的前馈回路。结肠中的基质成纤维细胞群体由异质和不同的细胞亚型组成，其在结肠炎和结肠癌的发展中起关键作用。在这里，作者产生了IL-11报告小鼠，并表征了结肠炎和结肠癌临床前模型中炎性IL-11+成纤维细胞的起源和表型。
Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment. The stromal fibroblast population in the colon is composed of heterogeneous and distinct cell subtypes that play a crucial role in the development of colitis and colon cancer. Here the authors generate IL-11 reporter mice and characterize the origin and phenotype of inflammatory IL-11+ fibroblasts in colitis and colon cancer preclinical models.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
9.7
作者：
Lacroix, M;Siwek, B;Body, JJ
通讯作者：
Body, JJ
影响因子：
14.2
作者：
Molet, S;Hamid, Q;Chakir, J
通讯作者：
Chakir, J
影响因子：
3.6
作者：
KIMURA, Y;YANAGIMACHI, R
通讯作者：
YANAGIMACHI, R
影响因子：
50.3
作者：
Calon A;Espinet E;Palomo-Ponce S;Tauriello DV;Iglesias M;Céspedes MV;Sevillano M;Nadal C;Jung P;Zhang XH;Byrom D;Riera A;Rossell D;Mangues R;Massagué J;Sancho E;Batlle E
通讯作者：
Batlle E