Caveolin-1 Mediates Inflammatory Breast Cancer Cell Invasion via the Akt1 Pathway and RhoC GTPase
Caveolin-1 Mediates Inflammatory Breast Cancer Cell Invasion via the Akt1 Pathway and RhoC GTPase
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DOI：
10.1002/jcb.25025
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发表时间：
2015-06-01
影响因子：
4
通讯作者：
van Golen, Kenneth L.
中科院分区：
文献类型：
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作者：
Joglekar, Madhura;Elbazanti, Weam O.;van Golen, Kenneth L.
炎症性乳腺癌（IBC）具有侵袭乳腺皮肤的真皮淋巴管并易于转移的倾向，可以说是最致命的乳腺癌。我们之前报道了小洞蛋白-1在IBC中过表达，并且RhoC GTPase是导致侵袭性表型的转移开关。rhoc驱动的侵袭需要Akt1的磷酸化。使用可靠的IBC细胞系，我们开始确定caveolin-1表达是否影响rhoc介导的IBC侵袭。小洞蛋白-1通过引入siRNA或小洞蛋白支架结构域而下调。检测细胞的侵袭能力，检测Akt1和RhoC GTPase的状态。下调caveolin-1可显著降低IBC细胞侵袭。当小窝蛋白-1下调时，Akt1的激活降低，导致RhoC GTPase磷酸化降低。因此，我们在这里报道，小窝蛋白-1过表达通过激活Akt1介导IBC细胞侵袭，Akt1磷酸化RhoC GTPase。(C) 2015 Wiley期刊公司
With a propensity to invade the dermal lymphatic vessels of the skin overlying the breast and readily metastasize, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. We previously reported that caveolin-1 is overexpressed in IBC and that RhoC GTPase is a metastatic switch responsible for the invasive phenotype. RhoC-driven invasion requires phosphorylation by Akt1. Using a reliable IBC cell line we set out to determine if caveolin-1 expression affects RhoC-mediated IBC invasion. Caveolin-1 was down regulated by introduction of siRNA or a caveolin scaffolding domain. The ability of the cells to invade was tested and the status of Akt1 and RhoC GTPase examined. IBC cell invasion is significantly decreased when caveolin-1 is down regulated. Activation of Akt1 is decreased when caveolin-1 is down regulated, leading to decreased phosphorylation of RhoC GTPase. Thus, we report here that caveolin-1 overexpression mediates IBC cell invasion through activation Akt1, which phosphorylates RhoC GTPase. (C) 2015 Wiley Periodicals, Inc.