Down Syndrome Candidate Region 1 Isoform 1L regulated tumor growth by targeting both angiogenesis and tumor cells.
Down Syndrome Candidate Region 1 Isoform 1L regulated tumor growth by targeting both angiogenesis and tumor cells.
复制标题
DOI：
10.1016/j.mvr.2021.104305
复制
发表时间：
2022-03
影响因子：
3.1
通讯作者：
Zeng, Huiyan
中科院分区：
文献类型：
--
作者：
Chen, Chen;Cui, Pengfei;Zhao, Kevin;Niu, Gengming;Hou, Shiqiang;Zhao, Dezheng;Zeng, Huiyan
血管生成对于实体肿瘤的生长是至关重要的，超过其最小尺寸。先前，我们报道了唐氏综合症候选区域1亚型1L(DSCR1-1L)是血管内皮生长因子和组胺诱导内皮细胞表达上调最多的基因之一，并调控内皮细胞的增殖、迁移和血管生成。然而，目前尚不清楚DSCR1-1L是否在肿瘤生长中发挥作用。在这项研究中，我们发现DSCR1-1L shRNAs显著抑制了小鼠移植黑色素瘤的生长及其相关的肿瘤血管生成。在功能获得分析中，在小鼠内皮细胞中过表达DSCR1-1L基因足以显著增加致癌物诱导的肿瘤起始率、异种肿瘤的生长以及我们的内皮表达的DSCR1-1L转基因小鼠的肿瘤转移，并诱导血管生成。首次发现DSCR1-1L在多种肿瘤细胞中也有表达。DSCR1-1L shRNAs抑制肿瘤细胞的增殖和迁移，但增加DSCR1-1L基因的过表达。最近，我们报道了DSCR1-1L通过下调VE-钙粘附素的表达来调节血管生成。在此，我们发现DSCR1-1L下调了E-钙粘蛋白的表达。因此，DSCR1-1L通过下调(V)E-钙粘附素来调节血管内皮细胞和肿瘤细胞，是治疗癌症的极佳靶点。DSCR1-1L shRNAs具有临床应用的潜力。
Angiogenesis is critical for solid tumor growth beyond its minimal size. Previously, we reported that Down Syndrome Candidate Region 1 isoform 1L (DSCR1–1L) was one of the most up-regulated genes in endothelial cells induced by VEGF and histamine, and regulated endothelial cell proliferation, migration and angiogenesis. However, it was not known whether DSCR1–1L played a role in tumor growth. In this study, we found that DSCR1–1L shRNAs significantly inhibited the growth of transplanted melanoma in mice and its associated tumoral angiogenesis. In the gain of function assay, overexpression of DSCR1–1L cDNA in mouse endothelium is sufficient to significantly increase the tumor initiation induced by carcinogen, the growth of xenografted tumor, and the tumor metastasis in our endothelially-expressed DSCR1–1L transgenic mice, in which angiogenesis was induced. It was the first time to find that DSCR1–1L was also expressed in various tumor cells. DSCR1–1L shRNAs inhibited, but overexpression of DSCR1–1L cDNA increased, the tumor cell proliferation and migration. Most recently, we reported that DSCR1–1L modulated angiogenesis by down-regulation of VE-cadherin expression. Here, we found that DSCR1–1L down-regulated the expression of E-cadherin. Hence, DSCR1–1L is an excellent therapeutic target for cancers by regulation of both the endothelial and tumor cells through down-regulating (V)E-cadherin. DSCR1–1L shRNAs have the potential to be developed for clinical application.
登录
查看更多内容
DOI：
10.1084/jem.20091846
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Helfrich I;Scheffrahn I;Bartling S;Weis J;von Felbert V;Middleton M;Kato M;Ergün S;Augustin HG;Schadendorf D
通讯作者：
Schadendorf D
DOI：
10.1073/pnas.0708148104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Ebos, John M. L.;Lee, Christina R.;Kerbel, Robert S.
通讯作者：
Kerbel, Robert S.
影响因子：
4.8
作者：
Ermak, G;Morgan, TE;Davies, KJA
通讯作者：
Davies, KJA
影响因子：
4.8
作者：
Liu, Xin;Zhao, Dezheng;Zeng, Huiyan
通讯作者：
Zeng, Huiyan
影响因子：
4.7
作者：
Hayman, Suzanne R.;Leung, Nelson;Grande, Joseph P.;Garovic, Vesna D.
通讯作者：
Garovic, Vesna D.