2020年8月
Signal-transducing adapter protein-1 is required for maintenance of leukemic stem cells in CML.
Oncogene
- 巻
- 39
- 号
- 34
- 開始ページ
- 5601
- 終了ページ
- 5615
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41388-020-01387-9
- 出版者・発行元
- Springer Science and Business Media {LLC}
The family of signal-transducing adapter proteins (STAPs) has been reported to be involved in a variety of intracellular signaling pathways and implicated as transcriptional factors. We previously cloned STAP-2 as a c-Fms interacting protein and explored its effects on chronic myeloid leukemia (CML) leukemogenesis. STAP-2 binds to BCR-ABL, upregulates BCR-ABL phosphorylation, and activates its downstream molecules. In this study, we evaluated the role of STAP-1, another member of the STAP family, in CML pathogenesis. We found that the expression of STAP-1 is aberrantly upregulated in CML stem cells (LSCs) in patients' bone marrow. Using experimental model mice, deletion of STAP-1 prolonged the survival of CML mice with inducing apoptosis of LSCs. The impaired phosphorylation status of STAT5 by STAP-1 ablation leads to downregulation of antiapoptotic genes, Bcl-2 and Bcl-xL. Interestingly, transcriptome analyses indicated that STAP-1 affects several signaling pathways related to BCR-ABL, JAK2, and PPARγ. This adapter protein directly binds to not only BCR-ABL, but also STAT5 proteins, showing synergistic effects of STAP-1 inhibition and BCR-ABL or JAK2 tyrosine kinase inhibition. Our results identified STAP-1 as a regulator of CML LSCs and suggested it to be a potential therapeutic target for CML.
- リンク情報
-
- DOI
- https://doi.org/10.1038/s41388-020-01387-9
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/32661325
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441008
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000548100200003&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-85087783280&partnerID=MN8TOARS 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85087783280&origin=inward
- ID情報
-
- DOI : 10.1038/s41388-020-01387-9
- ISSN : 0950-9232
- eISSN : 1476-5594
- ORCIDのPut Code : 78223273
- PubMed ID : 32661325
- PubMed Central 記事ID : PMC7441008
- SCOPUS ID : 85087783280
- Web of Science ID : WOS:000548100200003