Annexin A1 regulates TGF-β signaling and promotes metastasis formation of basal-like breast cancer cells

被引:173
作者
de Graauw, Marjo [1 ]
van Miltenburg, Martine H. [1 ]
Schmidt, Marjanka K. [2 ]
Pont, Chantal [1 ]
Lalai, Reshma [1 ]
Kartopawiro, Joelle [1 ]
Pardali, Evangelia [3 ,4 ]
Le Devedec, Sylvia E. [1 ]
Smit, Vincent T. [5 ]
van der Wal, Annemieke [5 ]
Van't Veer, Laura J. [2 ]
Cleton-Jansen, Anne-Marie [5 ]
ten Dijke, Peter [3 ,4 ]
van de Water, Bob [1 ]
机构
[1] Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Toxicol, NL-2300 RA Leiden, Netherlands
[2] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands
[3] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RA Leiden, Netherlands
[4] Leiden Univ, Med Ctr, Ctr Biomed Genet, NL-2300 RA Leiden, Netherlands
[5] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; MAMMARY ADENOCARCINOMA; DOWN-REGULATION; EARLY ENDOSOMES; EXPRESSION; GENE; LINES; SUBTYPES; DIFFERENTIATION; INTERNALIZATION;
D O I
10.1073/pnas.0913360107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Annexin A1 (AnxA1) is a candidate regulator of the epithelial-to mesenchymal (EMT)-like phenotypic switch, a pivotal event in breast cancer progression. We show here that AnxA1 expression is associated with ahighly invasivebasal- likebreast cancer subtypeboth in apanel of human breast cancer cell lines as in breast cancer patients and that AnxA1 is functionally related to breast cancer progression. AnxA1 knockdownininvasivebasal- likebreast cancer cells reduced the number of spontaneous lung metastasis, whereas additional expression of AnxA1 enhanced metastatic spread. AnxA1 promotes metastasis formation by enhancingTGF beta/Smad signalingandactin reorganization, which facilitates an EMT-like switch, thereby allowing ef. cient cell migration and invasion of metastatic breast cancer cells.
引用
收藏
页码:6340 / 6345
页数:6
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