KISS1R signaling promotes invadopodia formation in human breast cancer cell via β-arrestin2/ERK
KISS1R signaling promotes invadopodia formation in human breast cancer cell via β-arrestin2/ERK
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DOI：
10.1016/j.cellsig.2015.12.010
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发表时间：
2016-03-01
影响因子：
4.8
通讯作者：
Bhattacharya, Moshmi
中科院分区：
文献类型：
--
作者：
Goertzen, Cameron G.;Dragan, Magdalena;Bhattacharya, Moshmi
Kisspeptins (KPs) 是 KISS) 基因的肽产物，是 Kisspeptin 受体 (KISS1R)（一种 G 蛋白偶联受体）的内源配体。在许多癌症中，KISS1R 信号传导发挥抗转移作用。然而，我们之前已经证明，在缺乏雌激素受体 (ER α) 的乳腺癌细胞中，kisspeptin-10 通过依赖 β-arrestin-2 的机制与表皮生长因子受体 (EGFR) 相互作用，刺激细胞迁移和侵袭。为了进一步明确 KISS1R 刺激侵袭的机制，我们确定了三阴性乳腺癌细胞中下调 KISS1R 表达的效果。我们发现 KISS1R 的消耗降低了它们的间充质表型和侵袭性。我们首次证明 KISS1R 信号传导诱导侵袭伪足形成以及关键侵袭伪足蛋白、皮质素、丝切蛋白和 I 型膜基质金属蛋白酶 (MT1-MMP) 的激活。此外，KISS1R 刺激的侵袭伪足形成是通过涉及 β 阻滞和 ERK1/2 依赖性机制的新途径发生的，独立于 Src 综上所述，我们的研究结果表明，针对 KISS1R 信号轴可能是抑制侵袭和转移的有前途的策略。 Crown 版权所有 (C) 2015 由 Elsevier Inc. 出版。保留所有权利。
Kisspeptins (KPs), peptide products of the KISS) gene are endogenous ligands for the kisspeptin receptor (KISS1R), a G protein-coupled receptor. In numerous cancers, KISS1R signaling plays anti-metastatic roles. However, we have previously shown that in breast cancer cells lacking the estrogen receptor (ER alpha), kisspeptin-10 stimulates cell migration and invasion by cross-talking with the epidermal growth factor receptor (EGFR), via a beta-arrestin-2-dependent mechanism. To further define the mechanisms by which KISS1R stimulates invasion, we determined the effect of down-regulating KISS1R expression in triple negative breast cancer cells. We found that depletion of KISS1R reduced their mesenchymal phenotype and invasiveness. We show for the first time that KISS1R signaling induces invadopodia formation and activation of key invadopodia proteins, cortactin, cofilin and membrane type I matrix metalloproteases (MT1-MMP). Moreover, KISS1R stimulated invadopodia formation occurs via a new pathway involving a beta-arresting and ERK1/2-dependent mechanism, independent of Src Taken together, our findings suggest that targeting the KISS1R signaling axis might be a promising strategy to inhibit invasiveness and metastasis. Crown Copyright (C) 2015 Published by Elsevier Inc. All rights reserved.