Colorectal cancer-associated fibroblasts promote metastasis by up-regulating LRG1 through stromal IL-6/STAT3 signaling

转移 癌症研究 癌相关成纤维细胞 间质细胞 上皮-间质转换 结直肠癌 医学 癌症 生物 内科学
作者
Beiping Zhong,Bing Cheng,Xiaoming Huang,Qian Xiao,Zhitong Niu,Yufeng Chen,Qiang Yu,Wenyu Wang,Xiaojian Wu
出处
期刊:Cell Death and Disease [Springer Nature]
卷期号:13 (1) 被引量:64
标识
DOI:10.1038/s41419-021-04461-6
摘要

Abstract Cancer-associated fibroblasts (CAFs) have been shown to play a strong role in colorectal cancer metastasis, yet the underlying mechanism remains to be fully elucidated. Using CRC clinical samples together with ex vivo CAFs-CRC co-culture models, we found that CAFs induce expression of Leucine Rich Alpha-2-Glycoprotein 1(LRG1) in CRC, where it shows markedly higher expression in metastatic CRC tissues compared to primary tumors. We further show that CAFs-induced LRG1 promotes CRC migration and invasion that is concomitant with EMT (epithelial-mesenchymal transition) induction. In addition, this signaling axis has also been confirmed in the liver metastatic mouse model which displayed CAFs-induced LRG1 substantially accelerates metastasis. Mechanistically, we demonstrate that CAFs-secreted IL-6 (interleukin-6) is responsible for LRG1 up-regulation in CRC, which occurs through a direct transactivation by STAT3 following JAK2 activation. In clinical CRC tumor samples, LRG1 expression was positively correlated with CAFs-specific marker, α-SMA, and a higher LRG1 expression predicted poor clinical outcomes especially distant metastasis free survival, supporting the role of LRG1 in CRC progression. Collectively, this study provided a novel insight into CAFs-mediated metastasis in CRC and indicated that therapeutic targeting of CAFs-mediated IL-6-STAT3-LRG1 axis might be a potential strategy to mitigate metastasis in CRC.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
烟花应助haifang采纳,获得10
2秒前
2秒前
中平完成签到 ,获得积分10
2秒前
张张完成签到,获得积分10
3秒前
二三发布了新的文献求助10
3秒前
aa123456y发布了新的文献求助10
3秒前
何必呢发布了新的文献求助10
4秒前
拼搏雁山发布了新的文献求助10
4秒前
kkdsseed发布了新的文献求助10
5秒前
研友_ZGDEG8完成签到,获得积分10
5秒前
hadfunsix完成签到 ,获得积分10
6秒前
liuyuanhao发布了新的文献求助10
8秒前
醫介蘇生完成签到,获得积分10
10秒前
酷波er应助jar7989采纳,获得10
10秒前
跳跃的半双完成签到,获得积分10
11秒前
奋斗的杰完成签到,获得积分10
12秒前
13秒前
科研通AI5应助郑恩熙采纳,获得10
14秒前
老猫完成签到,获得积分20
18秒前
科研通AI5应助LXG666采纳,获得10
19秒前
JamesPei应助天天喝咖啡采纳,获得10
20秒前
20秒前
王小玉发布了新的文献求助10
20秒前
21秒前
袁一亿完成签到,获得积分10
22秒前
23秒前
23秒前
完美世界应助二三采纳,获得10
24秒前
郑恩熙完成签到,获得积分10
24秒前
replay完成签到,获得积分10
24秒前
fal发布了新的文献求助200
25秒前
125mmD91T完成签到,获得积分10
27秒前
奋斗向南发布了新的文献求助10
27秒前
Jasper应助Suchen136采纳,获得10
27秒前
领导范儿应助驰驰采纳,获得10
28秒前
28秒前
29秒前
慕青应助老猫采纳,获得20
29秒前
replay发布了新的文献求助10
29秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Les Mantodea de Guyane Insecta, Polyneoptera 1000
Structural Load Modelling and Combination for Performance and Safety Evaluation 1000
Conference Record, IAS Annual Meeting 1977 820
England and the Discovery of America, 1481-1620 600
電気学会論文誌D(産業応用部門誌), 141 巻, 11 号 510
Exploring the effects of an evidenced-based professional development programme on teaching and learning in Chinese kindergartens 500
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3576516
求助须知:如何正确求助?哪些是违规求助? 3146501
关于积分的说明 9465459
捐赠科研通 2848050
什么是DOI,文献DOI怎么找? 1565422
邀请新用户注册赠送积分活动 733021
科研通“疑难数据库(出版商)”最低求助积分说明 719534