Expression levels of the metalloproteinase ADAM8 critically regulate proliferation, migration and malignant signalling events in hepatoma cells.

Published on Feb 1, 2021in Journal of Cellular and Molecular Medicine4.486
· DOI :10.1111/JCMM.16015
Tanzeela Awan1
Estimated H-index: 1
(RWTH Aachen University),
Aaron Babendreyer8
Estimated H-index: 8
(RWTH Aachen University)
+ 5 AuthorsAndreas Ludwig63
Estimated H-index: 63
(RWTH Aachen University)
Hepatocellular carcinoma (HCC) is one of the most common metastatic tumours. Tumour growth and metastasis depend on the induction of cell proliferation and migration by various mediators. Here, we report that the A Disintegrin and Metalloproteinase (ADAM) 8 is highly expressed in murine HCC tissues as well as in murine and human hepatoma cell lines Hepa1-6 and HepG2, respectively. To establish a dose-dependent role of different ADAM8 expression levels for HCC progression, ADAM8 expression was either reduced via shRNA- or siRNA-mediated knockdown or increased by using a retroviral overexpression vector. These two complementary approaches revealed that ADAM8 expression levels correlated positively with proliferation, clonogenicity, migration and matrix invasion and negatively with apoptosis of hepatoma cells. Furthermore, the analysis of pro-migratory and proliferative signalling pathways revealed that ADAM8 expression level was positively associated with expression of β1 integrin as well as with the activation of focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), Src kinase and Rho A GTPase. Finally, up-regulation of promigatory signalling and cell migration was also seen with a proteolytically inactive ADAM8 mutant. These findings reveal that ADAM8 is critically up-regulated in hepatoma cells contributes to cell proliferation and survival and furthermore induces pro-migratory signalling pathways independently of its proteolytic activity. By this, ADAM8 can promote cell functions most relevant for HCC growth and metastasis.
#1Aaron Babendreyer (RWTH Aachen University)H-Index: 8
#2Lisa Molls (RWTH Aachen University)H-Index: 2
Last. Andreas Ludwig (RWTH Aachen University)H-Index: 63
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// Tobias Pasqualon 1 , Jessica Pruessmeyer 1 , Vera Jankowski 2 , Aaron Babendreyer 1 , Esther Groth 1 , Julian Schumacher 1 , Andrea Koenen 1 , Sarah Weidenfeld 1 , Nicole Schwarz 3 , Bernd Denecke 4 , Holger Jahr 5 , Daniela Dreymueller 1 , Joachim Jankowski 2 , Andreas Ludwig 1 1 Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany 2 Institute of Molecular Cardiovascular Research, RWTH Aachen University, Aachen, Germany 3 Institute of Molecular and Cellular Anato...
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Cited By1
#1Tanzeela Awan (RWTH Aachen University)H-Index: 1
#2Aaron Babendreyer (RWTH Aachen University)H-Index: 8
Last. Andreas Ludwig (RWTH Aachen University)H-Index: 63
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Acute and chronic liver inflammation is driven by cytokine and chemokine release from various cell types in the liver. Here, we report that the induction of inflammatory mediators is associated with a yet undescribed upregulation of the metalloproteinase ADAM8 in different murine hepatitis models. We further show the importance of ADAM8 expression for the production of inflammatory mediators in cultured liver cells. As a model of acute inflammation, we investigated liver tissue from lipopolysacc...