Cathepsin L promotes angiogenesis by regulating the CDP/Cux/VEGF-D pathway in human gastric cancer.
Cathepsin L promotes angiogenesis by regulating the CDP/Cux/VEGF-D pathway in human gastric cancer.
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组织蛋白酶L通过调节CDP/Cux/VEGF-D通路促进人胃癌血管生成
DOI：
10.1007/s10120-020-01080-6
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Su L
中科院分区：
文献类型：
--
作者：
Pan T;Jin Z;Yu Z;Wu X;Chang X;Fan Z;Li F;Wang X;Li Z;Zhou Q;Li J;Liu B;Su L
越来越多的证据表明，血管生成在肿瘤进展中起着重要作用。组织蛋白酶L（CTSL）是一种内体蛋白水解酶，在促进肿瘤转移中的作用已被广泛认识。然而，CTSL促进胃癌（GC）血管生成的机制仍不清楚。在GC样品中评估CTSL的核表达水平。通过内皮细胞管形成分析、HUVEC迁移实验和鸡胚绒毛尿囊膜（CAM）实验观察CTSL对胃癌血管生成的影响。通过血管生成抗体阵列、Western blot、免疫共沉淀（Co-IP）和双荧光素酶报告基因分析CDP/Cux/VEGF-D通路的参与。在本研究中，我们发现，胃癌细胞核CTSL表达水平显著高于癌旁胃组织，是一个潜在的重要的临床预后因素。功能丧失和获得试验表明CTSL促进体外HUVEC细胞的小管形成和迁移。CAM实验也显示CTSL在体内促进GC的血管生成。机制分析表明，CTSL可水解CDP/Cux，产生生理相关的p110亚型，p110亚型与VEGF-D稳定结合，促进VEGF-D的转录，从而促进GC的血管生成。本研究结果表明，CTSL在人胃癌血管生成的调节中起着建设性的作用，并可能成为胃癌的潜在治疗靶点。本文的在线版本（10.1007/s10120-020-01080-6）包含补充材料，可供授权用户使用。
Increasing evidence indicates that angiogenesis plays an important role in tumor progression. The function of cathepsin L (CTSL), an endosomal proteolytic enzyme, in promoting tumor metastasis is well recognized. The mechanisms by which CTSL has promoted the angiogenesis of gastric cancer (GC), however, remains unclear. The nuclear expression levels of CTSL were assessed in GC samples. The effects of CTSL on GC angiogenesis were determined by endothelial tube formation analysis, HUVEC migration assay, and chick embryo chorioallantoic membrane (CAM) assay. The involvement of the CDP/Cux/VEGF-D pathway was analyzed by angiogenesis antibody array, Western blot, co-immunoprecipitation (Co-IP) and dual-luciferase reporter assay. In this study, we found that the nuclear CTSL expression level in GC was significantly higher than that in adjacent nontumor gastric tissues and was a potential important clinical prognostic factor. Loss- and gain-of-function assays indicated that CTSL promotes the tubular formation and migration of HUVEC cells in vitro. The CAM assay also showed that CTSL promotes angiogenesis of GC in vivo. Mechanistic analysis demonstrated that CTSL can proteolytically process CDP/Cux and produce the physiologically relevant p110 isoform, which stably binds to VEGF-D and promotes the transcription of VEGF-D, thus contributing to the angiogenesis of GC. The findings of the present study suggested that CTSL plays a constructive role in the regulation of angiogenesis in human GC and could be a potential therapeutic target for GC. The online version of this article (10.1007/s10120-020-01080-6) contains supplementary material, which is available to authorized users.
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消化道癌症中的组织蛋白酶
影响因子：
--
作者：
Chen S;Dong H;Yang S;Guo H
通讯作者：
Guo H
DOI：
10.1016/j.biopha.2018.05.148
发表时间：
2018-09
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
--
作者：
Patel S;Homaei A;El-Seedi HR;Akhtar N
通讯作者：
Akhtar N
影响因子：
50.5
作者：
Bernards, N.;Creemers, G. J.;Lemmens, V. E. P. P.
通讯作者：
Lemmens, V. E. P. P.
影响因子：
3.1
作者：
Lu, Hong-Jie;Yan, Jing;Zheng, Yuan-Lin
通讯作者：
Zheng, Yuan-Lin
影响因子：
3.7
作者：
Haugen MH;Johansen HT;Pettersen SJ;Solberg R;Brix K;Flatmark K;Maelandsmo GM
通讯作者：
Maelandsmo GM