<p>Retinoic acid receptor &alpha; facilitates human colorectal cancer progression via Akt and MMP2 signaling</p>

Abstract

Purpose: Retinoic acid α (RARα) is overexpressed in various tumors and facilitates cancer progression. Although RARα has been shown to facilitate colorectal cancer (CRC) progression, more efforts to characterize mechanisms of RARα in CRC are needed in order to develop better target-based drugs for tumor therapy. Methods: RARα expression in CRC was assessed by IHC. EdU, QPCR, Western blotting, dual-luciferase reporter assay and ChIP were performed to explore the role of RARα in CRC and the mechanism involoved. Results: Here, we show an overexpression of RARα in 73.5% (i.e., 25 of 34 human CRC specimens). RARα 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, RARα facilitates CRC growth through Akt signaling activation to cause levels of PCNA to be upregulated. Furthermore, RARα 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 RARα via an enhanced Akt signaling and by increasing MMP2 transcription. CRC therapy can examine the use of RARα as a prospective molecular target.

Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas

“…Most of the aforementioned DMR regulated genes were not previously discovered for EPN relapses. Their potential as relapse driver genes was further enhanced by the fact that many of them, including CACNA1H 56 , SLC12A7 57 , CSPG4 58 , 59 , RARA 60 in RELA , and HSPB8 61 , ITGB4 62 , FAT1 63 , 64 in PFA tumors, have previously been associated with human cancers or ependymoma tumor dependency gene ( CACNA1H ) 11 , 65…”

ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

“…Xiang et al 32 found that the ERα-36-STAT3 complex could directly bind to the promoter regions of MMP2/9 and promote their expression in breast cancer cells. In another study, ChIP analyses indicated that MMP2 transcription was directly regulated by RARα 33 . We revealed in this study that ELTD1 could activate the luciferase activity of MMP2 in CRC cells.…”

MMP2 Polymorphisms and Colorectal Cancer Susceptibility in a Chinese Han Population

“… 24 Moreover, changes in MMP2 expression are related to the occurrence and development of CRC. For example, retinoic acid α promotes CRC carcinogenesis by increasing MMP2 transcription, 25 and seven transmembrane domains containing 1 (ELTD1/ADGRL4) can promote CRC cell migration and invasion by activating MMP2 at the transcriptional level. 11 Furthermore, TWIST1/2 can bind to the MMP2 promoter and induce its expression, resulting in increased epithelial-to-mesenchymal transition and invasion potential of CRC cells.…”