Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer.
Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer.
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钙和 TRPV4 通过 RhoA/ROCK1 通路调节细胞骨架促进子宫内膜癌转移
DOI：
10.1038/s41419-020-03181-7
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发表时间：
2020-11-23
影响因子：
9
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Li X;Cheng Y;Wang Z;Zhou J;Jia Y;He X;Zhao L;Dong Y;Fan Y;Yang X;Shen B;Wu X;Wang J;Xiong C;Wei L;Li X;Wang J
瞬时受体电位香草酸4（TRPV 4）是一种钙渗透性阳离子通道，与几种类型的癌症有关。然而，其生物学意义以及其在子宫内膜癌（EC）中的相关机制仍不清楚。在这项研究中，我们研究了钙在EC中的功能，特别关注TRPV 4及其下游途径。我们在此报道了高水平的血清离子钙与晚期EC进展显著相关的发现，并且在所有钙通道中，TRPV 4发挥了重要作用，高水平的TRPV 4表达与体外和体内的癌症进展相关。蛋白质组学和生物信息学分析表明，TRPV 4参与细胞骨架调控和Rho蛋白通路，调控EC细胞迁移。机制研究表明，TRPV 4和钙离子内流通过RhoA/ROCK 1途径作用于细胞骨架，最终激活LIMK/cofilin，从而影响F-actin和paxillin（PXN）水平。总体而言，我们的研究结果表明，离子血清钙水平与不良结局显着相关，应针对钙通道TRPV 4来改善EC的治疗和预防策略。
Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable cation channel that has been associated with several types of cancer. However, its biological significance, as well as its related mechanism in endometrial cancer (EC) still remains elusive. In this study, we examined the function of calcium in EC, with a specific focus on TRPV4 and its downstream pathway. We reported here on the findings that a high level of serum ionized calcium was significantly correlated with advanced EC progression, and among all the calcium channels, TRPV4 played an essential role, with high levels of TRPV4 expression associated with cancer progression both in vitro and in vivo. Proteomic and bioinformatics analysis revealed that TRPV4 was involved in cytoskeleton regulation and Rho protein pathway, which regulated EC cell migration. Mechanistic investigation demonstrated that TRPV4 and calcium influx acted on the cytoskeleton via the RhoA/ROCK1 pathway, ending with LIMK/cofilin activation, which had an impact on F-actin and paxillin (PXN) levels. Overall, our findings indicated that ionized serum calcium level was significantly associated with poor outcomes and calcium channel TRPV4 should be targeted to improve therapeutic and preventive strategies in EC.
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DOI：
10.1097/ppo.0000000000000312
发表时间：
2018
期刊：
Cancer journal (Sudbury, Mass.)
影响因子：
--
作者：
Hope JM;Greenlee JD;King MR
通讯作者：
King MR
影响因子：
2.9
作者：
Amano, Mutsuki;Nakayama, Masanori;Kaibuchi, Kozo
通讯作者：
Kaibuchi, Kozo
DOI：
10.1073/pnas.1715998115
发表时间：
2018-03-20
影响因子：
11.1
作者：
Di Modugno F;Caprara V;Chellini L;Tocci P;Spadaro F;Ferrandina G;Sacconi A;Blandino G;Nisticò P;Bagnato A;Rosanò L
通讯作者：
Rosanò L
硝苯地平通过 Beclin1 和 mTOR 通路诱导子宫内膜癌细胞自噬
影响因子：
6.1
作者：
Bao Xiao-xia;Xie Bu-shan;Wang Jian-liu
通讯作者：
Wang Jian-liu
影响因子：
6.6
作者：
Janssen, Dick A. W.;Hoenderop, Joost G.;Schalken, Jack A.
通讯作者：
Schalken, Jack A.