Matrix rigidity differentially regulates invadopodia activity through ROCK1 and ROCK2.
Matrix rigidity differentially regulates invadopodia activity through ROCK1 and ROCK2.
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DOI：
10.1016/j.biomaterials.2016.01.028
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发表时间：
2016-04
期刊：
影响因子：
14
通讯作者：
Parekh A
中科院分区：
文献类型：
--
作者：
Jerrell RJ;Parekh A
由于肿瘤微环境中的ECM刚性，ROCK活性增加，并通过肌动球蛋白收缩促进恶性表型。侵袭性迁移是由富含肌动蛋白的粘着性突起促进的，称为侵过性突起，可降解ECM。invadopdia的活性依赖于基质刚度和收缩力，这表明机械因素可能通过依赖岩石的肌动球蛋白收缩性来调节这些亚细胞结构。然而，新出现的证据表明，ROCK1和ROCK2亚型在细胞中发挥不同的功能，这表明可能有其他机制潜在地调节刚性依赖的侵入性活动。在这项研究中，我们发现基质刚性在癌细胞中驱动ROCK信号传导，但ROCK1和ROCK2通过不同的信号通路，通过收缩（NM II）和非收缩（LIMK）机制，差异地调节浸润细胞活性。这些数据表明，肿瘤微环境的机械刚性可能通过不同的途径驱动ROCK信号传导，从而增强癌症进展和转移所需的侵袭性迁移。
ROCK activity increases due to ECM rigidity in the tumor microenvironment and promotes a malignant phenotype via actomyosin contractility. Invasive migration is facilitated by actin-rich adhesive protrusions known as invadopodia that degrade the ECM. Invadopodia activity is dependent on matrix rigidity and contractile forces suggesting that mechanical factors may regulate these subcellular structures through ROCK-dependent actomyosin contractility. However, emerging evidence indicates that the ROCK1 and ROCK2 isoforms perform different functions in cells suggesting that alternative mechanisms may potentially regulate rigidity-dependent invadopodia activity. In this study, we found that matrix rigidity drives ROCK signaling in cancer cells but that ROCK1 and ROCK2 differentially regulate invadopodia activity through separate signaling pathways via contractile (NM II) and non-contractile (LIMK) mechanisms. These data suggest that the mechanical rigidity of the tumor microenvironment may drive ROCK signaling through distinct pathways to enhance the invasive migration required for cancer progression and metastasis.