Piezo1 Mechano-Activation Is Augmented by Resveratrol and Differs between Colorectal Cancer Cells of Primary and Metastatic Origin.
Piezo1 Mechano-Activation Is Augmented by Resveratrol and Differs between Colorectal Cancer Cells of Primary and Metastatic Origin.
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DOI：
10.3390/molecules27175430
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发表时间：
2022-08-25
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影响因子：
--
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癌细胞必须在循环中的异常流体剪切应力（FSS）中存活以转移。在此，我们研究了FSS对结直肠癌细胞凋亡、增殖、膜损伤、钙内流和治疗增敏的作用。我们使用来自同一患者的SW480（原发性肿瘤）和SW620细胞（淋巴结转移）对此进行了测试。将细胞暴露于剪切脉冲，模拟湍流区域中观察到的高FSS的毫秒间隔，或持续剪切以模拟循环肿瘤细胞经历的平均幅度。SW480细胞对FSS诱导的死亡比它们的转移对应物更敏感。剪切脉冲引起显著的细胞膜损伤，而恒定剪切降低细胞增殖并增加CD133的表达。为了研究机械敏感离子通道的作用，我们用Piezo1激动剂Yoda1处理细胞，增加细胞内钙。白藜芦醇预处理进一步增加钙内流通过脂质筏共定位的Piezo1。然而，如通过细胞凋亡的计算模型所预测的，由于钙饱和，观察到细胞凋亡的最小变化。此外，与SW620细胞相比，SW480细胞具有增加的Piezo1、钙内流和TRAIL介导的凋亡水平，突出了转移细胞的机械活化的差异，这可能是体内成功传播的必要因素。
Cancer cells must survive aberrant fluid shear stress (FSS) in the circulation to metastasize. Herein, we investigate the role that FSS has on colorectal cancer cell apoptosis, proliferation, membrane damage, calcium influx, and therapeutic sensitization. We tested this using SW480 (primary tumor) and SW620 cells (lymph node metastasis) derived from the same patient. The cells were exposed to either shear pulses, modeling millisecond intervals of high FSS seen in regions of turbulent flow, or sustained shear to model average magnitudes experienced by circulating tumor cells. SW480 cells were significantly more sensitive to FSS-induced death than their metastatic counterparts. Shear pulses caused significant cell membrane damage, while constant shear decreased cell proliferation and increased the expression of CD133. To investigate the role of mechanosensitive ion channels, we treated cells with the Piezo1 agonist Yoda1, which increased intracellular calcium. Pretreatment with resveratrol further increased the calcium influx via the lipid-raft colocalization of Piezo1. However, minimal changes in apoptosis were observed due to calcium saturation, as predicted via a computational model of apoptosis. Furthermore, SW480 cells had increased levels of Piezo1, calcium influx, and TRAIL-mediated apoptosis compared to SW620 cells, highlighting differences in the mechano-activation of metastatic cells, which may be a necessary element for successful dissemination in vivo.
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影响因子：
6
作者：
Dombroski JA;Hope JM;Sarna NS;King MR
通讯作者：
King MR
影响因子：
9.8
作者：
Albeck JG;Burke JM;Spencer SL;Lauffenburger DA;Sorger PK
通讯作者：
Sorger PK
DOI：
10.1097/ppo.0000000000000312
发表时间：
2018
期刊：
Cancer journal (Sudbury, Mass.)
影响因子：
--
作者：
Hope JM;Greenlee JD;King MR
通讯作者：
King MR
DOI：
10.1083/jcb.200708010
发表时间：
2008-03-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Idone V;Tam C;Goss JW;Toomre D;Pypaert M;Andrews NW
通讯作者：
Andrews NW
影响因子：
4.6
作者：
Alvarado-Estrada K;Marenco-Hillembrand L;Maharjan S;Mainardi VL;Zhang YS;Zarco N;Schiapparelli P;Guerrero-Cazares H;Sarabia-Estrada R;Quinones-Hinojosa A;Chaichana KL
通讯作者：
Chaichana KL