Retinoic acid receptor α facilitates human colorectal cancer progression via Akt and MMP2 signaling
Retinoic acid receptor α facilitates human colorectal cancer progression via Akt and MMP2 signaling
复制标题
视黄酸受体 α 通过 Akt 和 MMP2 信号传导促进人类结直肠癌进展
DOI：
10.2147/ott.s200261
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Shen, Dong-Yan
中科院分区：
文献类型：
--
作者：
Huang, Gui-Li;Chen, Qing-Xi;Shen, Dong-Yan
目的：视黄酸α（RAR α）在各种肿瘤中过表达，并促进癌症进展。虽然RAR α已被证明是促进结直肠癌（CRC）的进展，更多的努力来表征CRC中RAR α的机制，以开发更好的靶向药物用于肿瘤therapy.Methods：RAR α在CRC中的表达进行了评估IHC。通过EdU、QPCR、Western blotting、双荧光素酶报告基因检测和ChIP等方法，探讨RAR α在CRC中的作用及其机制。25/34例人CRC标本）。RAR α敲低降低细胞增殖、迁移和侵袭。这种表型表现可能与Akt的活化降低以及PCNA（增殖细胞核抗原）和MMP 2（基质金属肽酶）的表达相关。从机制上讲，RAR α通过Akt信号传导激活促进CRC生长，从而导致PCNA水平上调。结论：RAR α通过增强Akt信号通路和MMP 2的转录，促进大肠癌细胞的迁移和侵袭。CRC治疗可以检查RAR α作为前瞻性分子靶点的使用。
Purpose: Retinoic acid alpha (RAR alpha) is overexpressed in various tumors and facilitates cancer progression. Although RAR alpha has been shown to facilitate colorectal cancer (CRC) progression, more efforts to characterize mechanisms of RAR alpha in CRC are needed in order to develop better target-based drugs for tumor therapy.Methods: RAR alpha expression in CRC was assessed by IHC. EdU, QPCR, Western blotting, dual-luciferase reporter assay and ChIP were performed to explore the role of RAR alpha in CRC and the mechanism involoved.Results: Here, we show an overexpression of RAR alpha in 73.5% (i.e., 25 of 34 human CRC specimens). RAR alpha knockdown decreased cell proliferation, migration, and invasion. Such phenotypic manifestations can be correlated to lowered activation of Akt and expression of PCNA (proliferating cell nuclear antigen) as well as MMP2 (matrix metallopeptidase). Mechanistically, RAR alpha facilitates CRC growth through Akt signaling activation to cause levels of PCNA to be upregulated. Furthermore, RAR alpha promotes migration and invasion of CRC cells by directly recruiting the MMP2 promoter to enhance the expression of MMP2.Conclusions: These findings demonstrate that CRC carcinogenesis is promoted by RAR alpha via an enhanced Akt signaling and by increasing MMP2 transcription. CRC therapy can examine the use of RAR alpha as a prospective molecular target.