Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling
Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling
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DOI：
10.1242/jcs.194803
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发表时间：
2016-12-15
影响因子：
4
通讯作者：
Rowat, Amy C.
中科院分区：
文献类型：
--
作者：
Kim, Tae-Hyung;Gill, Navjot Kaur;Rowat, Amy C.
癌细胞的侵袭是转移的关键步骤。文献中一个过于简单的观点是，癌细胞变得更具侵袭性，就会变得更容易变形。β -肾上腺素能受体（β AR）信号驱动侵袭和转移，但对细胞变形性的影响尚不清楚。在这里，我们发现β - AR激动剂激活β -肾上腺素能信号传导降低了高度转移的人乳腺癌细胞的变形能力，并且这些较硬的细胞在体外更具侵袭性。我们发现β - AR激活也会降低卵巢、前列腺、黑色素瘤和白血病细胞的变形能力。在机制上，我们表明β ar介导的细胞硬化依赖于肌动蛋白细胞骨架和肌球蛋白II活性。这些细胞变形能力的改变可以通过药物阻断或基因敲除β 2-肾上腺素能受体来预防。我们的研究结果确定β(2)-肾上腺素能- ca2 +-肌动蛋白轴是细胞变形性的新调节剂，并表明细胞力学特性和侵袭之间的关系可能取决于环境。
Invasion by cancer cells is a crucial step in metastasis. An oversimplified view in the literature is that cancer cells become more deformable as they become more invasive. beta-adrenergic receptor (beta AR) signaling drives invasion and metastasis, but the effects on cell deformability are not known. Here, we show that activation of beta-adrenergic signaling by beta AR agonists reduces the deformability of highly metastatic human breast cancer cells, and that these stiffer cells are more invasive in vitro. We find that beta AR activation also reduces the deformability of ovarian, prostate, melanoma and leukemia cells. Mechanistically, we show that beta AR-mediated cell stiffening depends on the actin cytoskeleton and myosin II activity. These changes in cell deformability can be prevented by pharmacological beta-blockade or genetic knockout of the beta 2-adrenergic receptor. Our results identify a beta(2)-adrenergic-Ca2+- actin axis as a new regulator of cell deformability, and suggest that the relationship between cell mechanical properties and invasion might be dependent on context.