Rhophilin-associated tail protein 1 promotes migration and metastasis in triple negative breast cancer via activation of RhoA
Rhophilin-associated tail protein 1 promotes migration and metastasis in triple negative breast cancer via activation of RhoA
复制标题
Rhophilin相关尾蛋白1通过激活RhoA促进三阴性乳腺癌的迁移和转移
DOI：
10.1096/fj.201903281r
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发表时间：
2020-05-19
期刊：
影响因子：
4.8
通讯作者：
Lin, Chuyong
中科院分区：
文献类型：
--
作者：
Liu, Qinghua;Huang, Xinjian;Lin, Chuyong
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，具有促进转移的高运动和侵袭能力。了解TNBC的运动机制可能会提供新的肿瘤靶向脆弱性。在此，我们发现Rhophilin相关尾蛋白1（ROPN 1）在人TNBC细胞系和组织中选择性过表达。ROPN 1的过表达促进TNBC细胞的稳健迁移、侵袭和体内转移，而ROPN 1的沉默抑制TNBC细胞的稳健迁移、侵袭和体内转移。此外，我们发现ROPN 1通过rhophilin-1（RHPN 1）激活RhoA信号传导，导致TNBC细胞中肌动蛋白应力纤维形成增强。RhoA信号传导被证明对于ROPN 1介导的TNBC细胞的迁移和转移是必不可少的。最后，我们发现高水平的ROPN 1与乳腺癌患者的远处转移显著相关，并预测预后不良。这些发现揭示了TNBC细胞高运动性和转移的新机制，表明ROPN 1可能是潜在的预后标志物和治疗靶点。
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with high motile and invasive capacity that contributes to metastasis. Understanding the mechanisms for the motility of TNBC might provide novel targetable vulnerabilities of the tumors. Herein, we find that Rhophilin-associated tail protein 1 (ROPN1) is selectively overexpressed in human TNBC cell lines and tissues. Overexpression of ROPN1 promotes, while silencing of ROPN1 inhibits the robust migration, invasion, and in vivo metastasis of TNBC cells. Moreover, we find that ROPN1 activates RhoA signaling via rhophilin-1 (RHPN1), leading to enhanced actin stress fibers formation in TNBC cells. RhoA signaling is demonstrated to be essential for ROPN1-mediated migration and metastasis of TNBC cells. Finally, we find that high levels of ROPN1 are significantly associated distant metastasis and predicted poor prognosis in patients with breast cancer. These findings reveal a novel mechanism for the high motility and metastasis of TNBC cells, suggesting that ROPN1 might be a potential prognostic marker and therapeutic target.