p21-activated kinase 4 regulates HIF-1 alpha translation in cancer cells

Abstract

The p21-activated kinases (Paks) interact with Rac/Cdc42 GTPases to regulate the actin cytoskeleton as well as various signaling pathways. Although activation of Paks in many human cancers is known to mediate cancer progression, the role of Pak proteins in hypoxia is poorly understood. In this study, we found that both Pakl and Pak4 are highly expressed in HeLa cervical cancer cells, but only Pak4 knockdown attenuates expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in hypoxia. We further discovered that Pak4 regulates HIF-l alpha translation via the Akt-mTOR-4E-BP1 pathway under hypoxic conditions. These results support a novel connection between HIF-la and Pak4 in hypoxic cancer cells, and provide insights into mechanisms whereby tumors respond to and thrive under oxygen-deficient conditions. (C) 2017 Elsevier Inc. All rights reserved.