ADAMTS10 inhibits aggressiveness via JAK/STAT/c-MYC pathway and reprograms macrophage to create an anti-malignant microenvironment in gastric cancer
ADAMTS10 inhibits aggressiveness via JAK/STAT/c-MYC pathway and reprograms macrophage to create an anti-malignant microenvironment in gastric cancer
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ADAMTS10 通过 JAK/STAT/c-MYC 通路抑制侵袭性并重新编程巨噬细胞以在胃癌中创建抗恶性微环境
DOI：
10.1007/s10120-022-01319-4
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发表时间：
2022-08
期刊：
影响因子：
7.4
通讯作者：
Zuli Yang
中科院分区：
文献类型：
--
作者：
Junyi Zhou;Tuoyang Li;Hao Chen;Yingming Jiang;Y;ong Zhao;Jintuan Huang;Zijian Chen;Xiaocheng Tang;Zhenze Huang;Zuli Yang
具有血小板反应蛋白基序的去整合素和金属蛋白酶10（ADAMTS 10）在细胞外基质中起作用，并与Weill-Marchesani综合征相关。然而，其在胃癌中的作用仍然未知。本研究采用免疫组化和定量RT-PCR（qRT-PCR）方法检测ADAMTS 10在胃癌组织中的表达。通过体外和体内功能实验观察ADAMTS 10对胃癌细胞增殖的抑制作用。流式细胞仪检测ADAMTS 10对胃癌细胞周期、凋亡及活性氧的影响。Western blot检测ADAMTS 10的靶点。Western blot、qRT-PCR和流式细胞术检测ADAMTS 10对THP 1的影响。胃癌组织中ADAMTS 10表达下调，低水平表达的患者生存率低。ADAMTS 10过表达改变细胞周期，促进凋亡，抑制增殖，迁移和侵袭在体外和体内。ADAMTS 10通过JAK/STAT/c-MYC途径调节TXNIP和ROS。降低TXNIP和ROS可逆转ADAMTS 10对细胞迁移和侵袭的抑制作用。GC细胞分泌的ADAMTS 10可被THP 1吸收，并调节THP 1中的TXNIP和ROS。胃癌细胞分泌的ADAMTS 10可抑制巨噬细胞M2极化，提示ADAMTS 10通过JAK/STAT/c-MYC途径靶向TXNIP和ROS，在胃癌的进展和巨噬细胞极化中起重要作用，提示ADAMTS 10可能是胃癌潜在的生存标志物。
A disintegrin and metalloproteinase with thrombospondin motifs 10 (ADAMTS10) plays a role in extracellular matrix and correlates with Weill-Marchesani syndrome. However, its role in gastric cancer remains unknown. Thus, we started this research to unveil the role of ADAMTS10 in gastric cancer (GC).The expression of ADAMTS10 in GC was analyzed by immunohistochemical staining and quantitative RT-PCR (qRT-PCR). The effects of ADAMTS10 inhibiting GC cell progression were conducted by functional experiments in vitro and in vivo. Flow cytometry was used to discover changing of cell cycle, apoptosis and ROS by ADAMTS10 in GC cell. Western blot was applied to identify targets of ADAMTS10. Western blot, qRT-PCR and flow cytometry were applied to discover the effect of ADAMT10 on THP1.ADAMTS10 expression was downregulated in GC tissue and patients with low ADAMTS10 levels had poorer overall survival. ADAMTS10 overexpression altered cell cycle, promoted apoptosis, and inhibited proliferation, migration, and invasion in vitro and in vivo. ADAMTS10 regulated TXNIP and ROS through the JAK/STAT/c-MYC pathway. Decreasing TXNIP and ROS reversed the inhibitory effect of ADAMTS10 on cell migration and invasion in vitro. ADAMTS10 secreted by GC cells was absorbed by THP1 and regulated TXNIP and ROS in THP1. ADAMTS10 secreted by GC cells inhibited macrophage M2 polarization.These results suggest that ADAMTS10 targets TXNIP and ROS via the JAK/STAT/c-MYC pathway and that may play important roles in GC progression and macrophage polarization which indicates that ADAMTS10 can be a potential survival marker for gastric cancer.
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ADAMTS19 通过 NF-κB 通路靶向 S100A16，抑制人类胃癌中的细胞迁移和侵袭
影响因子：
5.5
作者：
Jiang Y;Yu X;Zhao Y;Huang J;Li T;Chen H;Zhou J;Huang Z;Yang Z
通讯作者：
Yang Z
DOI：
10.1016/j.matbio.2018.06.002
发表时间：
2018-10
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
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作者：
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Apte SS
影响因子：
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作者：
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Troeberg L
影响因子：
4.4
作者：
Clark, ME;Kelner, GS;Maki, RA
通讯作者：
Maki, RA
影响因子：
11.2
作者：
Jeon, JH;Lee, KN;Choi, I
通讯作者：
Choi, I