title: Loss of ERα induces amoeboid-like migration of breast cancer cells by downregulating vinculin.
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.
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Juliang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Wangqian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Shuning
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002465:Cell Movement; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D016596:Vinculin / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D016596:Vinculin