Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model.
Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model.
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DOI：
10.1242/dmm.010835
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发表时间：
2013-05
影响因子：
4.3
通讯作者：
Levin M
中科院分区：
文献类型：
--
作者：
Chernet BT;Levin M
了解将细胞行为协调成生物体内适当模式的组织和器官的机制是预防，检测和治疗癌症的基本要素。生物电信号（所有细胞中的静息跨膜电压电位梯度）是一组重要且广泛保守的调控模式形成的控制机制的基础。我们测试了跨膜电位在非洲爪蟾典型癌基因介导的肿瘤发生中的作用。去极化膜电位（VELF）是由Gli 1、KrasG 12 D、Xrel 3或p53 Trp 248过表达产生的诱导肿瘤样结构（ITLS）的特征。这种生物电特征也存在于前体ITLS位点中。VEGFR 2是一种生物电标记物，可在ITLS在组织学和形态学上变得明显之前揭示它们。此外，电压在功能上是重要的：超极化离子转运蛋白的过度表达导致恢复正常VEGF-I，并显着减少ITLS的形成在体内。为了表征VEGFR 2变化调节ITLS表型的分子机制，我们进行了抑制筛选。VmemB超极化通过VmemB调节的SLC 5A 8（一种先前与人类癌症有关的丁酸钠交换剂）的活性转导到下游事件中。这些数据表明，丁酸，组蛋白脱乙酰酶（HDAC）抑制剂，可能是负责转录事件介导的抑制ITLS的超极化。VEGFR 2是一种方便的细胞参数，通过它可以在体内检测由人类癌基因诱导的肿瘤，并代表了一种新的诊断模式。此外，静息膜电位的控制在功能上参与了携带癌基因的细胞偏离正常形态发生程序形成肿瘤的过程。调节VEGF-C水平是一种新的和有前途的肿瘤正常化策略。
Understanding mechanisms that orchestrate cell behavior into appropriately patterned tissues and organs within the organism is an essential element of preventing, detecting and treating cancer. Bioelectric signals (resting transmembrane voltage potential gradients in all cells) underlie an important and broadly conserved set of control mechanisms that regulate pattern formation. We tested the role of transmembrane potential in tumorigenesis mediated by canonical oncogenes in Xenopus laevis. Depolarized membrane potential (Vmem) was a characteristic of induced tumor-like structures (ITLSs) generated by overexpression of Gli1, KrasG12D, Xrel3 or p53Trp248. This bioelectric signature was also present in precursor ITLS sites. Vmem is a bioelectric marker that reveals ITLSs before they become histologically and morphologically apparent. Moreover, voltage was functionally important: overexpression of hyperpolarizing ion transporters caused a return to normal Vmem and significantly reduced ITLS formation in vivo. To characterize the molecular mechanism by which Vmem change regulates ITLS phenotypes, we performed a suppression screen. Vmem hyperpolarization was transduced into downstream events via Vmem-regulated activity of SLC5A8, a sodium-butyrate exchanger previously implicated in human cancer. These data indicate that butyrate, a histone deacetylase (HDAC) inhibitor, might be responsible for transcriptional events that mediate suppression of ITLSs by hyperpolarization. Vmem is a convenient cellular parameter by which tumors induced by human oncogenes can be detected in vivo and represents a new diagnostic modality. Moreover, control of resting membrane potential is functionally involved in the process by which oncogene-bearing cells depart from normal morphogenesis programs to form tumors. Modulation of Vmem levels is a novel and promising strategy for tumor normalization.
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影响因子：
3.6
作者：
Adams, Dany S.;Levin, Michael
通讯作者：
Levin, Michael
影响因子：
4.6
作者：
Åberg, P;Nicander, I;Ollmar, S
通讯作者：
Ollmar, S
DOI：
10.4161/cc.8.21.9888
发表时间：
2009-11-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Blackiston DJ;McLaughlin KA;Levin M
通讯作者：
Levin M
影响因子：
5.5
作者：
Becchetti, Andrea
通讯作者：
Becchetti, Andrea
影响因子：
11.2
作者：
Bandyopadhyay, D;Mishra, A;Medrano, EE
通讯作者：
Medrano, EE