Natriuretic peptide receptor a promotes gastric malignancy through angiogenesis process.
Natriuretic peptide receptor a promotes gastric malignancy through angiogenesis process.
复制标题
利钠肽受体a通过血管生成过程促进胃恶性肿瘤
DOI：
10.1038/s41419-021-04266-7
复制
发表时间：
2021-10-20
影响因子：
9
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Li Z;Fan H;Cao J;Sun G;Sen Wang;Lv J;Xuan Z;Xia Y;Wang L;Zhang D;Xu H;Xu Z
胃癌（GC）在全球癌症相关死亡率中排名第三，特别是在东亚。血管生成在促进肿瘤进展中起着重要作用，临床试验表明抗血管生成治疗在GC管理中是有效的。钠尿肽受体A（NPRA）在胃癌的发生、发展中起重要作用。NPRA是否能促进胃癌的血管生成尚不清楚。肿瘤标本收集及免疫组化实验显示NPRA的表达与CD 31的表达及血管密度呈正相关。体内和体外研究表明，NPRA可促进GC相关的血管生成和肿瘤转移。Co-IP/MS结果表明，NPRA可通过与HIF-1α结合而阻止HIF-1 α的降解。HIF-1α的保护作用提高了VEGF水平，从而促进了血管生成。总之，NPRA通过与HIF-1α结合保护HIF-1α免受蛋白水解，增加HIF-1α的表达，并促进GC血管生成。本研究发现了NPRA促进胃癌发生发展的新机制和HIF-1α的新调控机制。
Gastric cancer (GC) ranks the third among global cancer-related mortality, especially in East Asia. Angiogenesis plays an important role in promoting tumor progression, and clinical trials have demonstrated that anti-angiogenesis therapy is effective in GC management. Natriuretic peptide receptor A (NPRA) functions significantly in promoting GC development and progression. Whether NPRA can promote angiogenesis of GC remains unclear. Tumor samples collection and immunohistochemical experiment showed that the expression of NPRA was positively correlated with the expression of CD31 and vessel density. In vivo and in vitro analysis showed that NPRA could promote GC-associated angiogenesis and tumor metastasis. Results of Co-IP/MS showed that NPRA could prevent HIF-1α from being degraded by binding to HIF-1α. Protection of HIF-1α improved VEGF levels and thus promoted angiogenesis. In summary, NPRA protected HIF-1α from proteolysis by binding to HIF-1α, increased the expression of HIF-1α, and promoted GC angiogenesis. This study has discovered a new mechanism for NPRA to promote gastric cancer development and a new regulatory mechanism for HIF-1α.
登录
查看更多内容
DOI：
10.1111/j.1742-4658.2011.08083.x
发表时间：
2011-06
期刊：
The FEBS journal
影响因子：
--
作者：
Misono KS;Philo JS;Arakawa T;Ogata CM;Qiu Y;Ogawa H;Young HS
通讯作者：
Young HS
影响因子：
4.2
作者：
Pandey KN
通讯作者：
Pandey KN
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
7.4
作者：
Li, Zheng;Wang, Ji-Wei;Xu, Ze-Kuan
通讯作者：
Xu, Ze-Kuan