Extracellular matrix protein 1 recruits moesin to facilitate invadopodia formation and breast cancer metastasis
Extracellular matrix protein 1 recruits moesin to facilitate invadopodia formation and breast cancer metastasis
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细胞外基质蛋白 1 募集 moesin 促进侵袭伪足形成和乳腺癌转移
DOI：
10.1016/j.canlet.2018.08.022
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Qi, Zhongquan
中科院分区：
文献类型：
--
作者：
Wu, Qiuwan;Chen, Donghan;Qi, Zhongquan
侵袭伪足是肿瘤细胞基于肌动蛋白的皮质突起，并且是间质侵袭和转移所必需的。细胞外基质蛋白1（ECM 1）一直被认为是一种分泌性蛋白，但其在肿瘤细胞中的确切作用机制仍不清楚。最近发表的数据表明，ECM 1在重塑肌动蛋白细胞骨架的功能，然而，其在侵袭伪足形成的作用仍然未知。在这里，我们首次证明了ECM 1是一种膜蛋白，并且对于乳腺癌细胞的侵袭伪足形成至关重要。ECM 1耗竭减弱了肿瘤细胞的基质附着、侵袭和自发转移到小鼠肺的能力。此外，ECM 1和膜突蛋白（MSN）的共表达与侵袭性乳腺癌表型密切相关。ECM 1与MSN相互作用，并将其募集到膜附近，以促进MSN膜转位和磷酸化，从而促进乳腺癌细胞形成侵袭伪足。这些结果阐明了ECM 1在乳腺癌转移中的作用的新机制，并表明ECM 1作为克服肿瘤扩散的潜在治疗靶点。
Invadopodia are actin-based cortical protrusions of tumour cells, and required for stromal invasion and metastasis. Extracellular matrix protein 1 (ECM1) has long been regarded as a secretory protein, but the mechanism of its precise functions in tumour cells is still obscure. Recently published data suggested a function of ECM1 in remodelling the actin cytoskeleton; however, its role in invadopodia formation remains unknown. Here, we demonstrated for the first time that ECM1 was a membrane protein and was essential for invadopodia formation by breast cancer cells. ECM1 depletion attenuated the ability of tumour cells to matrix attachment, invasion, and spontaneous metastasis to the lungs of mice. Additionally, co-expression of ECM1 and moesin (MSN) was closely related to aggressive breast cancer phenotypes. ECM1 interacted with MSN and recruited it adjacent to the membrane in order to promote MSN membrane translocation and phosphorylation, which facilitated invadopodia formation by breast cancer cells. These results elucidate a novel mechanism underlying the role of ECM1 in breast cancer metastasis and suggest ECM1 as a potential therapeutic target for overcoming tumour dissemination.