イワモト　タカユキ   Takayuki Iwamoto   岩本　高行    所属   川崎医科大学  医学部 臨床医学　乳腺甲状腺外科学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	TIG1 promotes the development and progression of inflammatory breast cancer through activation of Axl kinase.
掲載誌名	正式名：Cancer research 略　 称：Cancer Res ISSNコード：15387445/00085472
掲載区分	国外
巻・号・頁	73(21),pp.6516-25
著者・共著者	Xiaoping Wang, Hitomi Saso, Takayuki Iwamoto, Weiya Xia, Yun Gong, Lajos Pusztai, Wendy A Woodward, James M Reuben, Steven L Warner, David J Bearss, Gabriel N Hortobagyi, Mien-Chie Hung, Naoto T Ueno
発行年月	2013/11
概要	Inflammatory breast cancer (IBC) is the most lethal form of breast cancer, but the basis for its aggressive properties are not fully understood. In this study, we report that high tumoral expression of TIG1 (RARRES1), a functionally undefined membrane protein, confers shorter survival in patients with IBC. TIG1 depletion decreased IBC cell proliferation, migration, and invasion in vitro and inhibited tumor growth of IBC cells in vivo. We identified the receptor tyrosine kinase, Axl, as a TIG1-binding protein. TIG1 interaction stablilized Axl by inhibiting its proteasome-dependent degradation. TIG1-depleted IBC cells exhibited reduced Axl expression, inactivation of NF-κB, and downregulation of matrix metalloproteinase-9, indicating that TIG1 regulates invasion of IBC cells by supporting the Axl signaling pathway in IBC cells. Consistent with these results, treatment of IBC cells with the Axl inhibitor SGI-7079 decreased their malignant properties in vitro. Finally, TIG1 expression correlated positively with Axl expression in primary human IBC specimens. Our findings establish that TIG1 positively modifies the malignant properties of IBC by supporting Axl function, advancing understanding of its development and rationalizing TIG1 and Axl as promising therapeutic targets in IBC treatment.
DOI	10.1158/0008-5472.CAN-13-0967
PMID	24014597