Loss of ERα induces amoeboid-like migration of breast cancer cells by downregulating vinculin

Yuan Gao, Zhaowei Wang, Qiang Hao, Weina Li, Yujin Xu, Juliang Zhang, Wangqian Zhang, Shuning Wang, Shuo Liu, Meng Li, Xiaochang Xue, Wei Zhang (), Cun Zhang () and Yingqi Zhang ()
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Yuan Gao: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Zhaowei Wang: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Qiang Hao: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Weina Li: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Yujin Xu: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Juliang Zhang: Xijing Hospital, The Fourth Military Medical University
Wangqian Zhang: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Shuning Wang: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Shuo Liu: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Meng Li: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Xiaochang Xue: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Wei Zhang: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Cun Zhang: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University
Yingqi Zhang: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract Oestrogen receptor alpha (ERα) is a well-known target of endocrine therapy for ERα-positive breast cancer. ERα-negative cells, which are enriched during endocrine therapy, are associated with metastatic relapse. Here we determine that loss of ERα in the invasive front and in lymph node metastasis in human breast cancer is significantly correlated with lymphatic metastasis. Using in vivo and in vitro experiments, we demonstrate that ERα inhibits breast cancer metastasis. Furthermore, we find that ERα is a novel regulator of vinculin expression in breast cancer. Notably, ERα suppresses the amoeboid-like movement of breast cancer cells by upregulating vinculin in 3D matrix, which in turn promotes cell–cell and cell–matrix adhesion and inhibits the formation of amoeboid-like protrusions. A positive association between ERα and vinculin expression is found in human breast cancer tissues. The results show that ERα inhibits breast cancer metastasis and suggest that ERα suppresses cell amoeboid-like movement by upregulating vinculin.

Date: 2017
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DOI: 10.1038/ncomms14483

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