Takayuki Iwamoto
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Breast and Thyroid Surgery,
   Position   Assistant Professor
Article types 原著
Language English
Peer review Peer reviewed
Title TIG1 promotes the development and progression of inflammatory breast cancer through activation of Axl kinase.
Journal Formal name：Cancer research
Abbreviation：Cancer Res
ISSN code：15387445/00085472
Domestic / ForeginForegin
Volume, Issue, Page 73(21),pp.6516-25
Author and coauthor 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
Publication date 2013/11
Summary 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