Kim Hyunju, Woo Dustin J, Kim So Yeon, Yang Eun Gyeong
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, KIST Campus, University of Science and Technology (UST), Seoul 02792, Republic of Korea.
Biochem Biophys Res Commun. 2017 Apr 29;486(2):270-276. doi: 10.1016/j.bbrc.2017.03.024. Epub 2017 Mar 10.
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 Pak1 and Pak4 are highly expressed in HeLa cervical cancer cells, but only Pak4 knockdown attenuates expression of hypoxia-inducible factor-1α (HIF-1α) in hypoxia. We further discovered that Pak4 regulates HIF-1α translation via the Akt-mTOR-4E-BP1 pathway under hypoxic conditions. These results support a novel connection between HIF-1α and Pak4 in hypoxic cancer cells, and provide insights into mechanisms whereby tumors respond to and thrive under oxygen-deficient conditions.
p21激活激酶（Paks）与Rac/Cdc42 GTP酶相互作用，以调节肌动蛋白细胞骨架以及各种信号通路。尽管已知在许多人类癌症中Paks的激活介导癌症进展，但Pak蛋白在缺氧中的作用却知之甚少。在本研究中，我们发现Pak1和Pak4在HeLa宫颈癌细胞中均高表达，但只有Pak4敲低能减弱缺氧条件下缺氧诱导因子-1α（HIF-1α）的表达。我们进一步发现，在缺氧条件下，Pak4通过Akt-mTOR-4E-BP1途径调节HIF-1α的翻译。这些结果支持了缺氧癌细胞中HIF-1α与Pak4之间的新联系，并为肿瘤在缺氧条件下做出反应并茁壮成长的机制提供了见解。
