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KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling

Author

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  • Jiong Li

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA)

  • Bo Yu

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA)

  • Peng Deng

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA)

  • Yingduan Cheng

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA)

  • Yongxin Yu

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA)

  • Kareena Kevork

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA)

  • Sivakumar Ramadoss

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA)

  • Xiangming Ding

    (David Geffen School of Medicine, UCLA)

  • Xinmin Li

    (David Geffen School of Medicine, UCLA)

  • Cun-Yu Wang

    (Laboratory of Molecular Signaling, School of Dentistry and Broad Stem Cell Research Center, UCLA
    Henry Samueli School of Engineering and Applied Science, UCLA)

Abstract

Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can self-renew and are highly tumorigenic and chemoresistant. While genetic mutations associated with human colorectal cancer development are well-known, little is known about how and whether epigenetic factors specifically contribute to the functional properties of human colorectal CSCs. Here we report that the KDM3 family of histone demethylases plays an important role in tumorigenic potential and survival of human colorectal CSCs by epigenetically activating Wnt target gene transcription. The depletion of KDM3 inhibits tumorigenic growth and chemoresistance of human colorectal CSCs. Mechanistically, KDM3 not only directly erases repressive H3K9me2 marks, but also helps to recruit histone methyltransferase MLL1 to promote H3K4 methylation, thereby promoting Wnt target gene transcription. Our results suggest that KDM3 is a critical epigenetic factor in Wnt signalling that orchestrates chromatin changes and transcription in human colorectal CSCs, identifying potential therapeutic targets for effective elimination of CSCs.

Suggested Citation

  • Jiong Li & Bo Yu & Peng Deng & Yingduan Cheng & Yongxin Yu & Kareena Kevork & Sivakumar Ramadoss & Xiangming Ding & Xinmin Li & Cun-Yu Wang, 2017. "KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15146
    DOI: 10.1038/ncomms15146
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    Cited by:

    1. Shuzhen Kuang & Katherine S. Pollard, 2024. "Exploring the roles of RNAs in chromatin architecture using deep learning," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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