1. Academic Validation
  2. Loss of ERα induces amoeboid-like migration of breast cancer cells by downregulating vinculin

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

  • Nat Commun. 2017 Mar 7;8:14483. doi: 10.1038/ncomms14483.
Yuan Gao 1 Zhaowei Wang 1 Qiang Hao 1 Weina Li 1 Yujin Xu 1 Juliang Zhang 2 Wangqian Zhang 1 Shuning Wang 1 Shuo Liu 1 Meng Li 1 Xiaochang Xue 1 Wei Zhang 1 Cun Zhang 1 Yingqi Zhang 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
  • 2 Department of Vascular and Endocrine Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
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.

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