Randall Division of Cell & Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, UK.
Cancer Division, King's College London, Guy's Campus, London SE1 1UL, UK.
Eur J Cell Biol. 2016 Nov;95(11):483-492. doi: 10.1016/j.ejcb.2016.07.002. Epub 2016 Jul 19.
Invadosomes are actin rich protrusive structures that facilitate invasive migration in multiple cell types. Comprised of invadopodia and podosomes, these highly dynamic structures adhere to and degrade the extracellular matrix, and are also thought to play a role in mechanosensing. Many extracellular signals have been implicated in invadosome stimulation, activating complex signalling cascades to drive the formation, activity and turnover of invadosomes. While the structural components of invadosomes have been well studied, the regulation of invadosome dynamics is still poorly understood. Protein kinases are essential to this regulation, affecting all stages of invadosome dynamics and allowing tight spatiotemporal control of their activity. Invadosome organisation and function have been linked to pathophysiological states such as cancer invasion and metastasis; therapeutic targeting of invadosome regulatory components is thus warranted. In this review, we discuss the involvement of kinase signalling in every stage of the invadosome life cycle and evaluate its significance.
侵袭小体是富含肌动蛋白的突起结构,可促进多种细胞类型的侵袭性迁移。侵袭小体由侵袭伪足和足突组成,这些高度动态的结构附着并降解细胞外基质,并且还被认为在机械感觉中发挥作用。许多细胞外信号已被牵连到侵袭小体的刺激中,激活复杂的信号级联反应以驱动侵袭小体的形成、活性和周转。虽然侵袭小体的结构成分已经得到了很好的研究,但侵袭小体动力学的调节仍知之甚少。蛋白激酶对这种调节至关重要,影响侵袭小体动力学的所有阶段,并允许对其活性进行紧密的时空控制。侵袭小体的组织和功能与癌症侵袭和转移等病理生理状态有关;因此,有必要针对侵袭小体调节成分进行治疗性靶向。在这篇综述中,我们讨论了激酶信号在侵袭小体生命周期的每个阶段的参与,并评估了其重要性。