2. Academic Validation
  3. Death-associated protein kinase 1 suppresses hepatocellular carcinoma cell migration and invasion by upregulation of DEAD-box helicase 20

Death-associated protein kinase 1 suppresses hepatocellular carcinoma cell migration and invasion by upregulation of DEAD-box helicase 20

  • Cancer Sci. 2020 Aug;111(8):2803-2813. doi: 10.1111/cas.14499.
Yide Huang 1 2,  Chenyi Wang 1 2,  Ke Li 2,  Yan Ye 2,  Aling Shen 3,  Libin Guo 2,  Pengchen Chen 1 2,  Chen Meng 2,  Qingshui Wang 1 2,  Xinliu Yang 2,  Zhen Huang 2,  Xiaohua Xing 4,  Youyu Lin 2,  Xiaolong Liu 4,  Jun Peng 3,  Yao Lin 1 2
Affiliations

Affiliations

  • 1 Central Laboratory at The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Collaborative Innovation Center for Rehabilitation Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
  • 2 Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.
  • 3 Fujian Key Laboratory of Integrative Medicine on Geriatric, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
  • 4 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
PMID: 32449268 DOI: 10.1111/cas.14499
Abstract

Death-associated protein kinase 1 (DAPK) is a calcium/Calmodulin kinase that plays a vital role as a suppressor gene in various cancers. Yet its role and target gene independent of p53 is still unknown in hepatocellular carcinoma (HCC). In this study, we discovered that DAPK suppressed HCC cell migration and invasion instead of proliferation or colony formation. Using a proteomics approach, we identified DEAD-box helicase 20 (DDX20) as an important downstream target of DAPK in HCC cells and critical for DAPK-mediated inhibition of HCC cell migration and invasion. Using Integrin inhibitor RGD and GTPase activity assays, we discovered that DDX20 suppressed HCC cell migration and invasion through the CDC42-integrin pathway, which was previously reported as an important downstream pathway of DAPK in Cancer. Further research using cycloheximide found that DAPK attenuates the proteasomal degradation of DDX20 protein, which is dependent on the kinase activity of DAPK. Our results shed light on new functions and regulation for both DAPK and DDX20 in carcinogenesis and identifies new potential therapeutic targets for HCC.

Keywords

DEAD-box helicase 20; death-associated protein kinase; hepatocellular carcinoma; invasion; migration; proteasome degradation.

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