Targeting SLITRK4 Restrains Proliferation and Liver Metastasis in Colorectal Cancer via Regulating PI3K/AKT/NFκB Pathway and Tumor‐Associated Macrophage

PI3K/AKT/mTOR通路 癌症研究 转移 结直肠癌 医学 蛋白激酶B 癌症 巨噬细胞 信号转导 内科学 生物 细胞生物学 生物化学 体外
作者
Xiaojiao Sun,Junling Zhang,Bingqi Dong,Qingqing Xiong,Xin Wang,Yanlun Gu,Zhiqi Wang,Huiyu Liu,Jixin Zhang,Xu He,Hongjin Liu,Yi Zhong,Chuxiao Yi,Xiaowei Chi,Zhenming Liu,Xiaocong Pang,Yimin Cui
出处
期刊:Advanced Science [Wiley]
标识
DOI:10.1002/advs.202400367
摘要

Abstract Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT‐ and NTRK‐like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients. Multiple in vitro and in vivo models suggested SLITRK4 promoted CRC tumorigenesis, invasion, migration, and angiogenesis, and inhibition of it restrained CRC tumor growth and liver metastasis with a more profound effect on the tumor microenvironment (TME). Mechanistically, SLITRK4 overexpression significantly activated the PI3K/AKT/NFκB pathway, regulated extracellular matrix organization, and multiple cytokines expression. Furthermore, the results from coculture models and single‐cell RNA sequencing analyses suggested SLITRK4 promoted tumor‐associated macrophages (TAMs) infiltration and polarization. In addition, macrophage depletion significantly inhibited SLITRK4‐induced liver metastasis in CRC. Finally, pharmacological inhibition of SLITRK4 by using lipid‐polymer hybrid nanoparticles (NPs) for systemic siRNA delivery can effectively inhibit CRC liver metastasis. Taken together, these results pinpoint that SLITRK4 regulates CRC tumorigenesis and liver metastasis, and siRNA delivering NPs agents validate the therapeutic potential of targeting SLITRK4 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
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
早发论文应助碳酸芙兰采纳,获得10
1秒前
1秒前
互助遵法尚德应助通~采纳,获得10
1秒前
teadan完成签到 ,获得积分10
1秒前
Beal Julien发布了新的文献求助10
2秒前
2秒前
粘豆包完成签到,获得积分10
4秒前
Tq发布了新的文献求助10
6秒前
7秒前
斯文败类应助窗外的你采纳,获得10
7秒前
8秒前
九秋霜完成签到,获得积分10
9秒前
动人的ccc完成签到,获得积分10
9秒前
Robin发布了新的文献求助10
9秒前
机智谷梦完成签到,获得积分10
10秒前
NVN_J完成签到,获得积分10
10秒前
小旭不会飞完成签到,获得积分10
11秒前
12秒前
dimysm发布了新的文献求助10
13秒前
14秒前
15秒前
科研小菜鸡完成签到,获得积分10
15秒前
15秒前
15秒前
16秒前
poyo完成签到,获得积分10
16秒前
李雨轩发布了新的文献求助10
16秒前
17秒前
18秒前
18秒前
恶恶么v发布了新的文献求助10
18秒前
20秒前
丘比特应助megan采纳,获得10
20秒前
帅气的凌寒完成签到,获得积分10
20秒前
清璃发布了新的文献求助10
20秒前
hy完成签到 ,获得积分10
21秒前
Robin完成签到,获得积分10
21秒前
yyyyyqy发布了新的文献求助10
21秒前
冷艳的白竹完成签到,获得积分10
21秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3155997
求助须知:如何正确求助?哪些是违规求助? 2807353
关于积分的说明 7872795
捐赠科研通 2465725
什么是DOI,文献DOI怎么找? 1312328
科研通“疑难数据库(出版商)”最低求助积分说明 630049
版权声明 601905