Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, 2300 RA, Leiden, The Netherlands.
Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6340-5. doi: 10.1073/pnas.0913360107. Epub 2010 Mar 22.
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 a highly invasive basal-like breast cancer subtype both in a panel of human breast cancer cell lines as in breast cancer patients and that AnxA1 is functionally related to breast cancer progression. AnxA1 knockdown in invasive basal-like breast cancer cells reduced the number of spontaneous lung metastasis, whereas additional expression of AnxA1 enhanced metastatic spread. AnxA1 promotes metastasis formation by enhancing TGFbeta/Smad signaling and actin reorganization, which facilitates an EMT-like switch, thereby allowing efficient cell migration and invasion of metastatic breast cancer cells.
膜联蛋白 A1（AnxA1）是上皮-间质（EMT）样表型转换的候选调节因子，这是乳腺癌进展中的一个关键事件。我们在这里表明，在一组人类乳腺癌细胞系和乳腺癌患者中，AnxA1 的表达与高度侵袭性的基底样乳腺癌亚型相关，并且 AnxA1 与乳腺癌的进展具有功能相关性。在侵袭性基底样乳腺癌细胞中敲低 AnxA1 可减少自发性肺转移的数量，而额外表达 AnxA1 则增强了转移的扩散。AnxA1 通过增强 TGFβ/Smad 信号和肌动蛋白重组来促进转移形成，从而促进 EMT 样转换，从而使转移性乳腺癌细胞能够有效地迁移和侵袭。
