CREPT facilitates colorectal cancer growth through inducing Wnt/β-catenin pathway by enhancing p300-mediated β-catenin acetylation

Yanquan Zhang, Shiyan Wang, Wei Kang, Chunxiao Liu, Yujuan Dong, Fangli Ren, Yinyin Wang, Jinglin Zhang, Guoping Wang, Ka Fai To, Xueji Zhang, Joseph Jy Sung, Zhijie Chang, Jun Yu

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3485-3500
Number of pages16
JournalOncogene
Volume37
Issue number26
DOIs
StatePublished - Jun 1 2018

Bibliographical note

Funding Information:
This project was supported by the National Natural Science Foundation (81301775, 81230044, 81572728), RGCGRF Hong Kong (14106415, 14111216, 14163817), 135 program project (2016YFC1303200), National Key Research and Development Program (2016YFA0500301); Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute

Funding Information:
Acknowledgements This project was supported by the National Natural Science Foundation (81301775, 81230044, 81572728), RGC-GRF Hong Kong (14106415, 14111216, 14163817), 135 program project (2016YFC1303200), National Key Research and Development Program (2016YFA0500301); Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute.

Publisher Copyright:
© 2018 The Author(s).

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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