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A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
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Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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RhoC GTPase Activation Assay
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HSP90α和KLK6共同调节压力诱导的前列腺癌细胞流动性

Katelyn L O'Neill, Johnny W Zigmond, Raymond Bergan

    bioRxiv : the preprint server for biology
    |January 9, 2026
    PubMed
    概括

    细胞应激令人惊地降低了前列腺癌细胞中的矩阵金属蛋白酶-2 (MMP-2) 活性. 细胞外热冲击蛋白90α (eHSP90α) 在抑制kallikrein相关酶6 (KLK6) 后恢复MMP-2活性至关重要.

    科学领域:

    • 在瘤学瘤学.
    • 分子生物学分子生物学
    • 细胞生物学 细胞生物学

    背景情况:

    • 前列腺癌 (PCa) 转移是由像矩阵金属蛋白酶-2 (MMP-2) 这样的蛋白酶调节的.
    • 细胞外热冲击蛋白90α (eHSP90α) 的增加与较高的MMP-2活性相关,但其在细胞应激中的作用尚不清楚.

    研究的目的:

    • 研究细胞应激对细胞外热冲击蛋白90α (eHSP90α) 和前列腺癌中矩阵金属蛋白酶-2 (MMP-2) 活性的影响.
    • 在压力条件下阐明调节MMP-2活性和细胞运动的机制.

    主要方法:

    • 人体前列腺细胞系受到压力,eHSP90α水平通过免疫块测量.
    • 使用光度凝脱和zymography评估了MMP活性.
    • 通过伤口愈合和Matrigel入侵试验量化细胞运动.
    • 使用CRISPR/Cas9创建HSP90α淘汰细胞进行进一步验证.

    主要成果:

    • 在所有测试的前列腺细胞系中,压力增加了eHSP90α,但降低了MMP-2活性.
    • 来自应激细胞的条件介质降低了非应激细胞的运动性.
    • 作为一种血清蛋白酶抑制剂的阿普罗丁尼能挽救了MMP-2的活性,但这种作用在HSP90α淘汰细胞中丧失了.

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  • 与卡利克林相关的酶6 (KLK6) 被确定为一种压力诱导的蛋白酶,它降低了MMP-2活性;它的淘汰恢复了MMP-2活性和细胞运动性.
  • 结论:

    • 一个新的压力诱导的细胞外网络调节MMP-2活动和前列腺癌细胞运动.
    • 卡利克林相关酶6 (KLK6) 是一种关键的压力诱导蛋白酶,可降低MMP-2活动和入侵.
    • 细胞外热冲击蛋白90α (eHSP90α) 在KLK6中和后拯救MMP-2活性方面发挥着关键作用.