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Transcriptional control and signal transduction, cell cycle

Nucleolin promotes Wnt signaling in human hematopoietic stem/progenitor cells

Leukemia volume 33, pages 1052–1054 (2019)Cite this article

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Nucleolin is an abundant multifunctional protein of growing and cancer cells, and a candidate target molecule for cancer therapy (reviewed in [1, 2]). It participates in gene transcription, RNA metabolism, cell-surface signaling, and cell proliferation (references in [1,2,3]). Nucleolin is enriched in hematopoietic stem/progenitor cells (HSPCs), as compared to differentiated hematopoietic tissue, and is aberrantly active in certain hematological neoplasms (references in [1, 4]). It promotes execution of the HSC gene expression program in HSPCs [3]. It also amplifies long-term culture-initiating cells and increases active β-catenin, active Akt, and Bcl-2 levels to sustain long-term, cytokine-dependent HSPC maintenance [4]. In addition to Wnts, certain non-Wnt factors can activate β-catenin [5]. Elaborating the relationship of nucleolin to stem cell signaling in hematopoiesis will increase understanding of HSPCs at the molecular level.

This study describes that, in human mobilized peripheral blood (MPB) HSPCs, nucleolin promotes Wnt and bone morphogenic protein (BMP) signaling. Furthermore, nucleolin counteracts GSK3β and is involved in the responsiveness to Wnt-3a that was implicated in HSPC function. The study provides new insights into molecular network relevant to stem/progenitor cells in normal and malignant hematopoiesis and suggests that nucleolin deregulation may contribute to stem cell signaling in leukemogenesis.

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References

  1. Grinstein E, Wernet P. Cellular signalling in normal and cancerous stem cells. Cell Signal. 2007;19:2428–33.

    Article  CAS  Google Scholar 

  2. Fujiki H, Watanabe T, Suganuma M. Cell-surface nucleolin acts as a central mediator for carcinogenic, anti-carcinogenic, and disease-related ligands. J Cancer Res Clin Oncol. 2014;140:689–99.

    Article  CAS  Google Scholar 

  3. Mahotka C, Bhatia S, Kollet J, Grinstein E. Nucleolin promotes execution of the hematopoietic stem cell gene expression program. Leukemia. 2018;32:1865–8.

    Article  CAS  Google Scholar 

  4. Bhatia S, Reister S, Mahotka C, Meisel R, Borkhardt A, Grinstein E. Control of AC133 / CD133 and impact on human hematopoietic progenitor cells through nucleolin. Leukemia. 2015;29:2208–20.

    Article  CAS  Google Scholar 

  5. Valenta T, Hausmann G, Basler K. The many faces and functions of β-catenin. EMBO J. 2012;31:2714–36.

    Article  CAS  Google Scholar 

  6. Ratajczak MZ. Spotlight series on stem cell mobilization: many hands on the ball, but who is the quarterback? Leukemia. 2010;24:1665–6.

    Article  CAS  Google Scholar 

  7. Luis TC, Ichii M, Brugman MH, Kincade P, Staal FJT. Wnt signaling strength regulates normal hematopoiesis and its deregulation is involved in leukemia development. Leukemia. 2012;26:414–21.

    Article  CAS  Google Scholar 

  8. McCubrey JA, Steelman L, Bertrand FE, Davis NM, Abrams SL, Montalto G, et al. Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention. Leukemia. 2014;28:15–33.

    Article  CAS  Google Scholar 

  9. Zylbersztejn F, Flores-Violante M, Voeltzel T, Nicolini FE, Lefort S, Maguer-Satta V. The BMP pathway: a unique tool to decode origin and progression of leukemia. Exp Hematol. 2018;61:36–4.

    Article  CAS  Google Scholar 

  10. Luis T, Naber B, Fibbe W, van Dongen J, Staal FJT. Wnt3a nonredundantly controls hematopoietic stem cell function and its deficiency results in complete absence of canonical Wnt signaling. Blood. 2010;116:496–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded, PI E. Grinstein, by Deutsche Forschungsgemeinschaft, grant GR 3581/2-1, and José Carreras Leukämie-Stiftung, grant DJCLS R 12/32.

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  1. These authors contributed equally: Sven Reister, Csaba Mahotka

Authors and Affiliations

  1. Medical Faculty, Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany

    Sven Reister & Edgar Grinstein

  2. Medical Faculty, Institute of Pathology, Heinrich Heine University, Düsseldorf, Germany

    Csaba Mahotka & Natascha van den Höfel

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  1. Sven Reister
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Correspondence to Edgar Grinstein.

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Reister, S., Mahotka, C., van den Höfel, N. et al. Nucleolin promotes Wnt signaling in human hematopoietic stem/progenitor cells. Leukemia 33, 1052–1054 (2019). https://doi.org/10.1038/s41375-019-0401-4

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