The P-Rex1/Rac signaling pathway as a point of convergence for HER/ErbB receptor and GPCR responses.
The P-Rex1/Rac signaling pathway as a point of convergence for HER/ErbB receptor and GPCR responses.
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DOI：
10.1080/21541248.2016.1221273
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发表时间：
2018-07-04
期刊：
影响因子：
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通讯作者：
Lopez-Haber, Cynthia
中科院分区：
文献类型：
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作者：
Kazanietz, Marcelo G;Barrio-Real, Laura;Lopez-Haber, Cynthia
鸟嘌呤核苷酸交换因子（GEF）负责介导特定小G蛋白（如Rac）的GDP/GTP交换。有大量证据表明Rac-GEFs参与控制癌细胞迁移和转移进展。我们先前已经确定Rac-GEF P-Rex 1是HER/ErbB受体和G-蛋白偶联受体（GPCR）CXCR 4下游乳腺癌细胞中肌动蛋白细胞骨架重排和细胞运动的介体。与正常乳腺组织相比，P-Rex 1在管腔A和B乳腺癌中高度表达，而在基底乳腺癌中表达非常低，并且其表达与患者中转移的出现相关。在这里，我们讨论了参与P-Rex 1作为致癌/转移性受体在乳腺癌中的效应，并强调其相关性的受体触发的运动信号的收敛。此外，我们还概述了我们最近的研究结果，描述了HER/ErbB受体和CXCR 4之间的串扰，以及这如何影响P-Rex 1/Rac 1信号的激活，并强调了未来的挑战。我们提出了一个模型，其中P-Rex 1作为一个关键节点的整合上游输入HER/ErbB受体和CXCR 4在管腔乳腺癌细胞。
Guanine nucleotide Exchange Factors (GEFs) are responsible for mediating GDP/GTP exchange for specific small G proteins, such as Rac. There has been substantial evidence for the involvement of Rac-GEFs in the control of cancer cell migration and metastatic progression. We have previously established that the Rac-GEF P-Rex1 is a mediator of actin cytoskeleton rearrangements and cell motility in breast cancer cells downstream of HER/ErbB receptors and the G-Protein Coupled Receptor (GPCR) CXCR4. P-Rex1 is highly expressed in luminal A and B breast cancer compared to normal mammary tissue, whereas expression is very low in basal breast cancer, and its expression correlates with the appearance of metastasis in patients. Here, we discuss the involvement of P-Rex1 as an effector of oncogenic/metastatic receptors in breast cancer and underscore its relevance in the convergence of receptor-triggered motile signals. In addition, we provide an overview of our recent findings describing a cross-talk between HER/ErbB receptors and CXCR4, and how this impacts on the activation of P-Rex1/Rac1 signaling, as well as highlight challenges that lie ahead. We propose a model in which P-Rex1 acts as a crucial node for the integration of upstream inputs from HER/ErbB receptors and CXCR4 in luminal breast cancer cells.