CXCL16 Promotes Gastric Cancer Tumorigenesis via ADAM10-Dependent CXCL16/CXCR6 Axis and Activates Akt and MAPK Signaling Pathways.
CXCL16 Promotes Gastric Cancer Tumorigenesis via ADAM10-Dependent CXCL16/CXCR6 Axis and Activates Akt and MAPK Signaling Pathways.
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CXCL16 通过 ADAM10 依赖性 CXCL16/CXCR6 轴促进胃癌肿瘤发生并激活 Akt 和 MAPK 信号通路
DOI：
10.7150/ijbs.57826
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发表时间：
2021
影响因子：
9.2
通讯作者：
Ji J
中科院分区：
文献类型：
--
作者：
Han J;Fu R;Chen C;Cheng X;Guo T;Huangfu L;Li X;Du H;Xing X;Ji J
CXC基序趋化因子配体16（CXC motif chemokine ligand 16，CXCL 16）的异常表达与肿瘤的进展和转移有关，是许多肿瘤的预后因子，其相对高表达可作为肿瘤进展的标志物。然而，其在胃癌（GC）发生发展和转移中的作用和机制尚不清楚。在我们的研究中，使用公共数据集和人GC组织样本来确定CXCL 16表达水平。我们的结果显示，CXCL 16在GC中上调。CXCL 16在胃癌中的高表达与胃癌的组织学分化程度和pTNM分期有关。CXCL 16的高表达与胃癌患者的不良生存率呈正相关。采用功能获得和丧失实验研究CXCL 16在体外和体内增殖和迁移中的生物学作用。基因集富集分析（Gene set enrichment analysis，GSEA）显示，上皮间质转化（epithelial-mesenchymal transition，EMT）、Akt和MAPK信号通路相关基因在高浓度CXCL 16组中显著富集，Western blot证实了这一点。CXCL 16的过表达促进了去整合素和金属蛋白酶（ADAM 10）和CXC基序趋化因子受体6（CXCR 6）的表达，并通过激活Akt和MAPK信号通路，介导了GC中CXCL 16/CXCR 6的正反馈环。在胃癌的发生发展过程中，敲除ADAM 10可阻断CXCL 16/CXCR 6轴。总之，我们的研究结果提供了深入的见解，CXCL 16通过增强ADAM 10依赖的CXCL 16/CXCR 6轴激活促进GC肿瘤的发生。
Abnormal expression of CXC motif chemokine ligand 16 (CXCL16) has been demonstrated to be associated with tumor progression and metastasis, served as a prognostic factor in many cancers, with higher relative expression behaving as a marker of tumor progression. However, its role and mechanisms underlying progression and metastasis of gastric cancer (GC) are yet to be elucidated. In our investigation, public datasets and human GC tissue samples were used to determine the CXCL16 expression levels. Our results revealed that CXCL16 was upregulated in GC. The high expression CXCL16 in GC was significantly associated with histologic poor differentiation and pTNM staging. And high CXCL16 was positively correlated with the poor survival of GC patients. Gain-and loss-of-function experiments were employed to investigate the biological role of CXCL16 in proliferation and migration both in vitro and in vivo. Mechanically, Gene set enrichment analysis (GSEA) revealed that the epithelial‑mesenchymal transition (EMT), Akt and MAPK signal pathway related genes were significantly enriched in the high CXCL16 group, which was confirmed by western blot. Moreover, overexpression CXCL16 promoted the disintegrin and metalloproteases (ADAM10) and the CXC motif chemokine receptor 6 (CXCR6) expression, which mediated the CXCL16/CXCR6 positive feedback loop in GC, with activating Akt and MAPK signaling pathways. Knocking down ADAM10 would interrupted the CXCL16/CXCR6 axis in the carcinogenesis and progression of GC. In conclusion, our findings offered insights into that CXCL16 promoted GC tumorigenesis by enhancing ADAM10-dependent CXCL16/CXCR6 axis activation.
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影响因子：
3.7
作者：
Raman D;Sobolik-Delmaire T;Richmond A
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