Shin Ik Jae, Park Bae Keun, Ahn Yong-Tae, Kim Yongkuk, An Won G
Joint Research Center of Pusan National University-Fraunhofer IGB, Busan 609-735, Korea.
Mol Med Rep. 2010 Sep-Oct;3(5):815-9. doi: 10.3892/mmr.2010.325. Epub 2010 Jul 8.
The intracellular actin cytoskeleton is a central player in tumor cell migration and adhesion, and interacts with the extracellular matrix during the progression to metastasis. Although recent reports on motility events have revealed that the destabilization of actin affects cancer progression and hypoxia inducible factor-1α (HIF-1α) activity, little is known about the responsive activity of HIF-1α following actin disruption. Here, we demonstrate that the inhibition of actin polymerization or depolymerization attenuates HIF-1α expression independently of proteasomal degradation. The disruption of actin dynamics inactivates HIF-1α translational expression through p70S6K translational signaling; this is independent of p53 activation, suggesting that actin dysfunction-mediated HIF-1α destabilization may lead to the development of novel anticancer chemotherapeutic targets.
细胞内肌动蛋白细胞骨架在肿瘤细胞迁移和黏附中起核心作用，并在转移进展过程中与细胞外基质相互作用。尽管最近关于运动事件的报道表明，肌动蛋白的不稳定会影响癌症进展和缺氧诱导因子-1α（HIF-1α）活性，但关于肌动蛋白破坏后HIF-1α的反应活性却知之甚少。在这里，我们证明肌动蛋白聚合或解聚的抑制可独立于蛋白酶体降解减弱HIF-1α表达。肌动蛋白动力学的破坏通过p70S6K翻译信号使HIF-1α翻译表达失活；这与p53激活无关，表明肌动蛋白功能障碍介导的HIF-1α不稳定可能导致新型抗癌化疗靶点的开发。
