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.
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ER α 的缺失通过下调纽蛋白诱导乳腺癌细胞的阿米巴样迁移
DOI：
10.1038/ncomms14483
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发表时间：
2017-03-07
影响因子：
16.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Gao Y;Wang Z;Hao Q;Li W;Xu Y;Zhang J;Zhang W;Wang S;Liu S;Li M;Xue X;Zhang W;Zhang C;Zhang Y
雌激素受体α (ERα)是雌激素受体α阳性乳腺癌内分泌治疗的一个众所周知的靶点。er α-阴性细胞在内分泌治疗过程中富集，与转移性复发有关。本研究发现，人乳腺癌浸润前部和淋巴结转移处ERα的缺失与淋巴转移密切相关。通过体内和体外实验，我们证明了ERα抑制乳腺癌转移。此外，我们发现ERα是乳腺癌中血管素表达的一种新的调节因子。值得注意的是，ERα通过上调三维基质中的血管素抑制乳腺癌细胞的阿米巴样运动，从而促进细胞间和细胞-基质的粘附，抑制阿米巴样突起的形成。在人乳腺癌组织中发现ERα和血管蛋白表达呈正相关。结果表明，ERα抑制乳腺癌转移，并提示ERα通过上调血管蛋白抑制细胞变形虫样运动。雌激素受体α (ERα)阴性细胞在内分泌治疗过程中富集，与乳腺癌的转移性复发有关。本文作者表明，ERα抑制乳腺癌转移，并提示ERα通过上调血管素抑制乳腺癌细胞的变形虫样迁移。
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. Estrogen receptor alpha (ERα)-negative cells, which are enriched during endocrine therapy, are associated with metastatic relapse of breast cancer. Here the authors show that ERα inhibits breast cancer metastasis and suggest that ERα suppresses the amoeboid-like migration of breast cancer cells by upregulating vinculin.