CXCR4 promotes neuroblastoma growth and therapeutic resistance through miR-15a/ 16-1–mediated ERK and BCL2/Cyclin D1 pathways
Cancer Research, ISSN: 1538-7445, Vol: 78, Issue: 6, Page: 1471-1483
2018
- 48Citations
- 44Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations48
- Citation Indexes48
- 48
- CrossRef43
- Captures44
- Readers44
- 44
Article Description
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.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85047788945&origin=inward; http://dx.doi.org/10.1158/0008-5472.can-17-0454; http://www.ncbi.nlm.nih.gov/pubmed/29259008; https://aacrjournals.org/cancerres/article/78/6/1471/633031/CXCR4-Promotes-Neuroblastoma-Growth-and; http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-17-0454; https://syndication.highwire.org/content/doi/10.1158/0008-5472.CAN-17-0454
American Association for Cancer Research (AACR)
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