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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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The role of NUMB/NUMB isoforms in cancer stem cells

  • Choi, Hye Yeon (Department of Molecular Microbiology and Immunology, University of Southern California) ;
  • Seok, Jaekwon (Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center (MCRC), Konkuk University) ;
  • Kang, Geun-Ho (Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center (MCRC), Konkuk University) ;
  • Lim, Kyung Min (Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center (MCRC), Konkuk University) ;
  • Cho, Ssang-Goo (Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center (MCRC), Konkuk University)
  • Received : 2021.03.18
  • Accepted : 2021.05.17
  • Published : 2021.07.31
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Abstract

Cancer stem cells (CSCs) are a subpopulation of cancer that can self-renew and differentiate into large tumor masses. Evidence accumulated to date shows that CSCs affect tumor proliferation, recurrence, and resistance to chemotherapy. Recent studies have shown that, like stem cells, CSCs maintain cells with self-renewal capacity by means of asymmetric division and promote cell proliferation by means of symmetric division. This cell division is regulated by fate determinants, such as the NUMB protein, which recently has also been confirmed as a tumor suppressor. Loss of NUMB expression leads to uncontrolled proliferation and amplification of the CSC pool, which promotes the Notch signaling pathway and reduces the expression of the p53 protein. NUMB genes are alternatively spliced to produce six functionally distinct isoforms. An interesting recent discovery is that the protein NUMB isoform produced by alternative splicing of NUMB plays an important role in promoting carcinogenesis. In this review, we summarize the known functions of NUMB and NUMB isoforms related to the proliferation and generation of CSCs.

Keywords

Acknowledgement

This paper was supported by Konkuk University Researcher Fund in 2019. This study was supported by grants from the National Research Foundation (NRF) funded by the Korean government (grant no. 2019M3A9H1030682 and NRF-2015R1A5A1009701). This paper was supported by Konkuk University Researcher Fund in 2019.

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