Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells.
Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells.
复制标题
离子通道TRPV4的激活诱导乳腺癌细胞中上皮向间充质转化。
DOI：
10.3390/ijms21249417
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发表时间：
2020-12-10
影响因子：
5.6
通讯作者：
Monteith GR
中科院分区：
文献类型：
--
作者：
Azimi I;Robitaille M;Armitage K;So CL;Milevskiy MJG;Northwood K;Lim HF;Thompson EW;Roberts-Thomson SJ;Monteith GR
上皮细胞到间充质细胞的转化（EMT）在肿瘤的耐药性和侵袭性中起重要作用。钙信号是乳腺癌细胞EMT诱导的关键。虽然抑制特定的钙透性离子通道可以调节乳腺癌细胞中EMT标志物的诱导，但目前尚不清楚特定钙通道的激活是否可以诱导EMT事件。在这项研究中，我们利用钙渗透离子通道TRPV4的选择性药理激活剂的可用性来评估钙内流在EMT标志物诱导中的直接作用。基因关联研究显示，在淋巴结阳性的基底乳腺癌中，TRPV4与EMT相关的基因本体和较差的无复发生存率之间存在联系。TRPV4是EMT诱导剂表皮生长因子（EGF）诱导MDA-MB-468乳腺癌细胞钙内流期的重要组成部分。然后，TRPV4的药理激活驱动了多种EMT标记物在乳腺癌细胞中的诱导。这些研究表明，钙通过特定途径流入似乎足以触发EMT事件。
Epithelial to mesenchymal transition (EMT) in cancer is important in therapeutic resistance and invasiveness. Calcium signaling is key to the induction of EMT in breast cancer cells. Although inhibition of specific calcium-permeable ion channels regulates the induction of a sub-set of EMT markers in breast cancer cells, it is still unclear if activation of a specific calcium channel can be a driver for the induction of EMT events. In this study, we exploited the availability of a selective pharmacological activator of the calcium-permeable ion channel TRPV4 to assess the direct role of calcium influx in EMT marker induction. Gene association studies revealed a link between TRPV4 and gene-ontologies associated with EMT and poorer relapse-free survival in lymph node-positive basal breast cancers. TRPV4 was an important component of the calcium influx phase induced in MDA-MB-468 breast cancer cells by the EMT inducer epidermal growth factor (EGF). Pharmacological activation of TRPV4 then drove the induction of a variety of EMT markers in breast cancer cells. These studies demonstrate that calcium influx through specific pathways appears to be sufficient to trigger EMT events.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
4.6
作者：
Azimi I;Petersen RM;Thompson EW;Roberts-Thomson SJ;Monteith GR
通讯作者：
Monteith GR
影响因子：
8
作者：
Adapala RK;Thoppil RJ;Ghosh K;Cappelli HC;Dudley AC;Paruchuri S;Keshamouni V;Klagsbrun M;Meszaros JG;Chilian WM;Ingber DE;Thodeti CK
通讯作者：
Thodeti CK
影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
MCUR1通过线粒体钙依赖性ROS/Nrf2/Notch通路促进肝细胞癌上皮-间质转化和转移
DOI：
10.1186/s13046-019-1135-x
发表时间：
2019-03-25
影响因子：
11.3
作者：
Jin, Mingpeng;Wang, Jiaojiao;Xing, Jinliang
通讯作者：
Xing, Jinliang