S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells
S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells
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DOI：
10.1080/15384101.2014.995495
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发表时间：
2015-02-15
期刊：
影响因子：
4.3
通讯作者：
Nylandsted, Jesper
中科院分区：
文献类型：
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作者：
Jaiswal, Jyoti K.;Nylandsted, Jesper
细胞的机械活动和细胞外环境对它们施加的应力是质膜（PM）损伤的恒定来源。在侵袭性肿瘤细胞中，增加的运动性与肿瘤基质的恶劣环境一起进一步增加PM损伤的风险。这些压力对肿瘤细胞质膜的影响和肿瘤细胞修复PM损伤的机制知之甚少。Ca 2+通过受损PM进入启动PM的修复。根据细胞类型的不同，不同的细胞器和蛋白质对这种Ca 2+进入做出反应，并促进受损质膜的修复。我们最近发现，在各种转移性癌症中表达的蛋白质，包括Ca 2+结合EF手蛋白S100 A11及其结合伴侣膜联蛋白A2，被肿瘤细胞用于质膜修复（PMR）。在这里，我们将讨论S100，膜联蛋白的蛋白质和它们的肌动蛋白细胞骨架的调节，导致PMR的参与。此外，我们将显示另一个S100成员-S100 A4积累在受伤的PM。这些发现揭示了S100和膜联蛋白在转移性癌症中上调的新作用，并将这些蛋白质和PMR鉴定为治疗转移性癌症的靶点。
Mechanical activity of cells and the stress imposed on them by extracellular environment is a constant source of injury to the plasma membrane (PM). In invasive tumor cells, increased motility together with the harsh environment of the tumor stroma further increases the risk of PM injury. The impact of these stresses on tumor cell plasma membrane and mechanism by which tumor cells repair the PM damage are poorly understood. Ca2+ entry through the injured PM initiates repair of the PM. Depending on the cell type, different organelles and proteins respond to this Ca2+ entry and facilitate repair of the damaged plasma membrane. We recently identified that proteins expressed in various metastatic cancers including Ca2+-binding EF hand protein S100A11 and its binding partner annexin A2 are used by tumor cells for plasma membrane repair (PMR). Here we will discuss the involvement of S100, annexin proteins and their regulation of actin cytoskeleton, leading to PMR. Additionally, we will show that another S100 member - S100A4 accumulates at the injured PM. These findings reveal a new role for the S100 and annexin protein up regulation in metastatic cancers and identify these proteins and PMR as targets for treating metastatic cancers.