CREPT facilitates colorectal cancer growth through inducing Wnt/β-catenin pathway by enhancing p300-mediated β-catenin acetylation
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摘要Using whole genome sequencing, we identified gene amplification of CREPT in colorectal cancer (CRC). In this study, we aim to clarify its clinical significance, biological effects, and mechanism in CRC. CREPT was upregulated in CRC cell lines and in 47.37% (72/152) of primary CRC tumors. Amplification of CREPT was detected in 48.28% (56/116) of primary CRC tumors, which was positively correlated with its overexpression (P < 0.001). Multivariate analysis showed that CRC patients with CREPT protein overexpression were significantly associated with poor disease-free survival (P < 0.05). CREPT significantly accelerated CRC cell proliferation and metastasis both in vitro and in vivo. RNA-sequencing (seq) analysis uncovered that the tumor-promoting effect by CREPT was attributed to enhancing Wnt/β-catenin signaling. Using co-immunoprecipitation coupled with mass spectroscopy, we identified p300 protein was a novel CREPT interacting partner. CREPT greatly increased the interaction between p300 and β-catenin, thus promoting p300-mediated β-catenin acetylation and stabilization. Moreover, CREPT cooperated with p300, leading to elevated active histone acetylation markers H3K27ac and H4Ac and decreased repressive histone marker H3K9me3 at the promoters of Wnt downstream targets. In summary, CREPT plays a pivotal oncogenic role in colorectal carcinogenesis through promoting Wnt/β-catenin pathway via cooperating with p300. CREPT may serve as a prognostic biomarker of patients with CRC.
出版社接受日期12.01.2018
著者Zhang Y, Wang S, Kang W, Liu C, Dong Y, Ren F, Wang Y, Zhang J, Wang G, To KF, Zhang X, Sung JJ, Chang Z, Yu J
期刊名稱Oncogene
出版年份2018
月份6
卷號37
期次26
頁次3485 - 3500
國際標準期刊號0950-9232
電子國際標準期刊號1476-5594
語言英式英語

上次更新時間 2020-06-08 於 03:39