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

Sekine, Y.; Ikeda, O.; Mizushima, A.; Ueno, Y.; Muromoto, R.; Yoshimura, A.; Kanakura, Y.; Oritani, K.; Matsuda, T.

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

Sekine, Y.; Ikeda, O.; Mizushima, A. et al.

Oncogene, 2012, 31(40), 4384-4396

Permalink : https://hdl.handle.net/2115/52665

このアイテムのアクセス数:1,298件（2026-08-09 04:02 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
Supplementary_information	pdf	146 KB	933	Supplementary Information
Supplementary_Figure_S1	pdf	574 KB	631	Supplementary Figure S1
Onc31-40_4384-4396	pdf	21.1 MB	1,280

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/52665
タイトル	STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis
著者	Sekine, Y. ; Ikeda, O. ; Mizushima, A. ; Ueno, Y. ; Muromoto, R. ; Yoshimura, A. ; Kanakura, Y. ; Oritani, K. ; Matsuda, T.
e-Rad_Researcher 20396295 著者名 Sekine, Y.
著者名 Ikeda, O.
著者名 Mizushima, A.
著者名 Ueno, Y.
e-Rad_Researcher 30455597 著者名 Muromoto, R.
著者名 Yoshimura, A.
著者名 Kanakura, Y.
著者名 Oritani, K.
e-Rad_Researcher 20212219 著者名 Matsuda, T.
言語	英語
キーワード	chronic myeloid leukemia
	BCR-ABL
	signal-transducing adaptor protein-2
	chemokine
	tumorigenesis
発行日	2012-10-04
出版者	Nature Publishing Group
収録物名	Oncogene
巻(号)	31(40)
ページ	4384-4396
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0950-9232
関連情報	PMID 22231445
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/onc.2011.604