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Amplified in breast cancer 1 promotes colorectal cancer progression through enhancing notch signaling

Oncogene volume 34, pages 3935–3945 (2015)Cite this article

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Abstract

Aberrant activation of Notch signaling has an essential role in colorectal cancer (CRC) progression. Amplified in breast cancer 1 (AIB1), also known as steroid receptor coactivator 3 or NCOA3, is a transcriptional coactivator that promotes cancer cell proliferation and invasiveness. However, AIB1 implication in CRC progression through enhancing Notch signaling is unknown. In this study, we found that several CRC cell lines expressed high levels of AIB1, and knockdown of AIB1 decreased cell proliferation, colony formation and tumorigenesis of these CRC cells. Specifically, knockdown of AIB1 inhibited cell cycle progression at G1 phase by decreasing the mRNA levels of cyclin A2, cyclin B1, cyclin E2 and hairy and enhancer of split (Hes) 1. Furthermore, AIB1 interacted with Notch intracellular domain and Mastermind-like 1 and was recruited to the Hes1 promoter to enhance Notch signaling. Downregulation of AIB1 also decreased CRC cell invasiveness in vitro and lung metastasis in vivo. Besides that, knockout of AIB1 in mice inhibited colon carcinogenesis induced by azoxymethane/dextran sodium sulfate treatment. The mRNA levels of cyclin B1 and Hes5 were downregulated, but p27, ATOH1 and MUC2 were upregulated in the colon tumors from AIB1-deficient mice compared with those from wild-type mice. Thus, our results signify the importance of AIB1 in CRC and demonstrate that AIB1 promotes CRC progression at least in part through enhancing Notch signaling, suggesting that AIB1 is a potential molecular target for CRC treatment.

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Acknowledgements

We thank Dr Dawang Zhou (Xiamen University) for providing HA-NICD, FLAG-NICD and Myc-NICD constructs, and Dr Lizhi Wu (University of Florida) for providing FLAG-MAML1 and pGL3-Hes1-promoter plasmids. This work was supported by grants from the National Natural Science Foundation of China (no. 81071671 and 31170819 to CY), the Fundamental Research Funds for the Central Universities (no. 2012121038 to CY), the New Teachers Award of the Ministry of Education (no. 20110121120004 to PM), and 111 Project B12001. JX is supported by the CA112403 and DK058242 NIH grants.

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  1. P Mo, Q Zhou and L Guan: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China

    P Mo, Q Zhou, L Guan, Y Wang, W Wang, M Miao, Z Tong, M Li, S Majaz, Y Liu & C Yu

  2. The First Affiliated Hospital of Xiamen University, Xiamen, China

    G Su

  3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    J Xu

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Correspondence to C Yu.

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Mo, P., Zhou, Q., Guan, L. et al. Amplified in breast cancer 1 promotes colorectal cancer progression through enhancing notch signaling. Oncogene 34, 3935–3945 (2015). https://doi.org/10.1038/onc.2014.324

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