ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human Gastric Cancer.
ADAMTS19 Suppresses Cell Migration and Invasion by Targeting S100A16 via the NF-κB Pathway in Human 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
DOI：
10.3390/biom11040561
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发表时间：
2021-04-12
期刊：
影响因子：
5.5
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Jiang Y;Yu X;Zhao Y;Huang J;Li T;Chen H;Zhou J;Huang Z;Yang Z
具有血小板反应蛋白基序的去整合素和金属蛋白酶19（ADAMTS 19）已被报道参与实体癌的发病机制。然而，其在胃癌（GC）中的作用仍然没有文献记载。采用免疫组化（IHC）染色和实时定量聚合酶链反应（qRT-PCR）对胃癌组织和癌旁正常组织进行检测，我们发现ADAMTS 19在胃癌组织中表达下调（IHC：p < 0.001; qRT-PCR：p = 0.017）。进一步的研究显示ADAMTS 19与远处转移（p = 0.008）和神经周围浸润（p = 0.018）相关，ADAMTS 19低的患者总体生存率更差（p = 0.021）。功能获得和丧失试验表明ADAMTS 19在体外抑制细胞迁移和侵袭。利用生物信息学分析和免疫共沉淀、免疫荧光和双荧光素酶报告基因分析，我们证实ADAMTS 19与细胞质P65结合，降低核因子κ-B（NF-κB）通路中关键转录因子P65的核磷酸化，从而下调S100钙结合蛋白A16（S100 A16）的表达。S100 A16作为ADAMTS 19的下游基因，在体外可逆转ADAMTS 19对细胞迁移和侵袭的抑制作用。ADAMTS 19和S100 A16的联合表达为胃癌提供了最佳的预后指标。ADAMTS 19高-S100 A16低患者的总生存期优于ADAMTS 19低-S100 A16高患者（p = 0.006）。这些结果表明，ADAMTS 19通过NF-κB途径靶向S100 A16抑制细胞迁移和侵袭，ADAMTS 19和S100 A16是GC的潜在转移和存活生物标志物。
A Disintegrin and Metalloproteinase with Thrombospondin motifs 19 (ADAMTS19) has been reported to participate in the pathogenesis of solid cancers. However, its role in gastric cancer (GC) remains undocumented. Using immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) on GC tissues and adjacent normal tissues, we found that ADAMTS19 was downregulated in GC tissues (IHC: p < 0.001; qRT-PCR: p = 0.017). Further investigation revealed that ADAMTS19 correlated with distant metastasis (p = 0.008) and perineural invasion (p = 0.018) and that patients with low ADAMTS19 had worse overall survival (p = 0.021). Gain- and loss-of-function assays showed that ADAMTS19 suppressed cell migration and invasion in vitro. Using bioinformatics analysis and co-immunoprecipitation, immunofluorescence, and dual-luciferase reporter gene assays, we confirmed that ADAMTS19 binds with cytoplasm P65, decreasing the nucleus phosphorylation of P65, a crucial transcription factor in the nuclear factor kappa-B (NF-κB) pathway, thereby downregulating S100 calcium-binding protein A16 (S100A16) expression. S100A16 acted as the downstream of ADAMTS19, reversing the suppression of cell migration and invasion by ADAMTS19 in vitro. A combination of ADAMTS19 and S100A16 expression provided the optimal prognostic indicator for GC. Patients with ADAMTS19high-S100A16low had better overall survival than ADAMTS19low-S100A16high patients (p = 0.006). These results suggest that ADAMTS19 suppresses cell migration and invasion by targeting S100A16 via the NF-κB pathway and that ADAMTS19 and S100A16 are potential metastasis and survival biomarkers for GC.
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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：
--
作者：
Mead TJ;Apte SS
通讯作者：
Apte SS
影响因子：
5.7
作者：
Alonso S;González B;Ruiz-Larroya T;Durán Domínguez M;Kato T;Matsunaga A;Suzuki K;Strongin AY;Gimènez-Bonafé P;Perucho M
通讯作者：
Perucho M
影响因子：
11
作者：
Zhou W;Pan H;Xia T;Xue J;Cheng L;Fan P;Zhang Y;Zhu W;Xue Y;Liu X;Ding Q;Liu Y;Wang S
通讯作者：
Wang S
影响因子：
3.1
作者：
Lv H;Hou H;Lei H;Nie C;Chen B;Bie L;Han L;Chen X
通讯作者：
Chen X
影响因子：
4.4
作者：
Koch A;De Meyer T;Jeschke J;Van Criekinge W
通讯作者：
Van Criekinge W