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STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis
| Title: | STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis |
| Authors: | Sekine, Y. Browse this author →KAKEN DB | | Ikeda, O. Browse this author | | Mizushima, A. Browse this author | | Ueno, Y. Browse this author | | Muromoto, R. Browse this author →KAKEN DB | | Yoshimura, A. Browse this author | | Kanakura, Y. Browse this author | | Oritani, K. Browse this author | | Matsuda, T. Browse this author →KAKEN DB |
| Keywords: | chronic myeloid leukemia | | BCR-ABL | | signal-transducing adaptor protein-2 | | chemokine | | tumorigenesis |
| Issue Date: | 4-Oct-2012 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Oncogene |
| Volume: | 31 |
| Issue: | 40 |
| Start Page: | 4384 |
| End Page: | 4396 |
| Publisher DOI: | 10.1038/onc.2011.604 |
| PMID: | 22231445 |
| Abstract: | In chronic myeloid leukemia (CML), the BCR-ABL fusion oncoprotein activates multiple pathways involved in cell survival, growth promotion and disease progression. In this report, we show that the signal transducing adaptor protein-2 (STAP-2) is involved in BCR-ABL activity. We demonstrate that STAP-2 bound to BCR-ABL, and BCR and ABL proteins, depending on the STAP-2 Src homology 2-like domain. BCR-ABL phosphorylates STAP-2 Tyr250 and the phosphorylated STAP-2 in turn up-regulated BCR-ABL phosphorylation, leading to enhanced activation of downstream signaling molecules including ERK, STAT5, BCL-xL and BCL-2. In addition, STAP-2 interacts with BCR-ABL to alter chemokine receptor expression leading to downregulation of CXCR4 and upregulation of CCR7. The interaction between STAP-2 and BCR-ABL plays a crucial role in conferring a growth advantage and resistance to imatinib, a BCR-ABL inhibitor, as well as tumor progression. Notably, mice injected with BCR-ABL/STAP-2-expressing Ba/F3 cells developed lymph node enlargement and hepatosplenomegaly. Moreover, suppression of STAP-2 in K562 CML cells resulted in no tumor formation in mice. Our results demonstrate a critical contribution of STAP-2 in BCR-ABL activity, and suggest that STAP-2 might be an important candidate for drug development for patients with CML. Further, the expression of STAP-2 provides useful information for estimating the characteristics of individual CML clones. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/52665 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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