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STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis

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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
signal-transducing adaptor protein-2
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)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 正

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