| Actin disruption inhibits hypoxia inducible factor-1α expression via inactivity of Mdm2-mediated p70S6K |
Authors: Ik Jae Shin, Bae Keun Park, Yong-Tae Ahn, Yongkuk Kim, Won G. An |
Affiliations: Joint Research Center of Pusan National University-Fraunhofer IGB, Busan 609-735, Korea, Institute of Basic Medical Science, Yonsei University Wonju College of Medicine, Gangwon 220-701, Korea, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA, Laboratory of Mathematical and Computational Biology, Department of Mathematics, Kyungpook National University, Daegu 702-701, Korea, School of Korean Medicine, Joint Research Center of Pusan National University-Fraunhofer IGB, Gyeongsangnam-do 626-870, Korea |
Published online on: Thursday, July 8, 2010 |
Doi: 10.3892/mmr.2010.325 |
Pages: 815-819 |
Abstract: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. |
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