Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

CXCR4 Promotes Neuroblastoma Growth and Therapeutic Resistance through miR-15a/16-1-Mediated ERK and BCL2/Cyclin D1 Pathways.

Author information

Affiliations

  • 1. Goldyne Savad Institute of Gene Therapy, Hebrew University Hospital, Jerusalem, Israel.
      Authors
    • Klein S 1
    • Dery E 1
    • Weiss ID 1
    • Barashi N 1
    • Abramovitch R 1
    • Harel Y 1
    • Olam D 1
    • Weiss L 1
    • Wald O 1
    • Galun E 1
    • Peled A 1, 2
    (11 authors)
  • 2. Biokine Therapeutics Ltd., Ness Ziona, Israel.
      Authors
    • Abraham M 2
    • Bulvik B 2
    • Wald H 2
    • Eizenberg O 2
    • Peled A 1, 2
    (5 authors)
  • 3. Hematology Division, Chaim Sheba Medical Center and Tel Aviv University, Tel-Hashomer, Israel.
      Authors
    • Beider K 3
    (1 author)
  • 4. BioLineRx Ltd., Modi'in, Israel.
      Authors
    • Pereg Y 4
    (1 author)

Cancer Research, 19 Dec 2017, 78(6):1471-1483
https://doi.org/10.1158/0008-5472.can-17-0454 PMID: 29259008 

Abstract 

CXCR4 expression in neuroblastoma tumors correlates with disease severity. In this study, we describe mechanisms by which CXCR4 signaling controls neuroblastoma tumor growth and response to therapy. We found that overexpression of CXCR4 or stimulation with CXCL12 supports neuroblastoma tumorigenesis. Moreover, CXCR4 inhibition with the high-affinity CXCR4 antagonist BL-8040 prevented tumor growth and reduced survival of tumor cells. These effects were mediated by the upregulation of miR-15a/16-1, which resulted in downregulation of their target genes BCL-2 and cyclin D1, as well as inhibition of ERK. Overexpression of miR-15a/16-1 in cells increased cell death, whereas antagomirs to miR-15a/16-1 abolished the proapoptotic effects of BL-8040. CXCR4 overexpression also increased miR-15a/16-1, shifting their oncogenic dependency from the BCL-2 to the ERK signaling pathway. Overall, our results demonstrate the therapeutic potential of CXCR4 inhibition in neuroblastoma treatment and provide a rationale to test combination therapies employing CXCR4 and BCL-2 inhibitors to increase the efficacy of these agents.Significance: These results provide a mechanistic rationale for combination therapy of CXCR4 and BCL-2 inhibitors to treat a common and commonly aggressive pediatric cancer.Cancer Res; 78(6); 1471-83. ©2017 AACR.

Full text links 

Read article at publisher's site: https://doi.org/10.1158/0008-5472.can-17-0454

Read article for free, from open access legal sources, via Unpaywall: https://aacr.figshare.com/articles/journal_contribution/Figure_S1_from_CXCR4_Promotes_Neuroblastoma_Growth_and_Therapeutic_Resistance_through_miR-15a_16-1_Mediated_ERK_and_BCL2_Cyclin_D1_Pathways/22417814/1/files/39863924.pdfUnpaywall

Citations & impact 

Impact metrics

34
Citations
Jump to Citations
5
Data citations
Jump to Data

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/34353623
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/34353623

Article citations

Go to all (34) article citations

Data 

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.