Enhanced OXER1 expression is indispensable for human cancer cell migration.

Abstract

OXER1 is a recently identified receptor, binding the arachidonic acid metabolic product 5-oxo-ETE, considered an inflammatory receptor, implicated in chemoattraction of circulating mononuclear cells, Ca2+ surge in neutrophils, inflammation and cancer. Recently, we have shown that OXER1 is also a membrane androgen receptor in various cancer tissues. It was reported that the presence of OXER1 in leucocytes and the production and release of 5-oxo-ETE by wounded tissues is a wound sensing mechanism, leading to lymphocyte attraction. In view of the similarity of hallmarks of cancer and wound healing, we have explored the role of OXER1 and its endogenous ligand in the control of cell migration of human cancer epithelial cells (DU-145, T47D and Hep3B), mimicking the activation/migration phase of healing. We show that OXER1 is up-regulated only at the leading edge of the wound and its expression is up-regulated by its ligand 5-oxo-ETE, in a time-related manner. Knock-down of OXER1 or inhibition of 5-oxo-ETE synthesis led to decreased migration of cells and a prolongation of healing, in culture prostate cancer cell monolayers, with a substantial modification of actin cytoskeleton and a decreased filopodia formation. Inhibition of cell migration is a phenomenon mediated by Gβγ OXER1 mediated actions. These results provide a novel mechanism of OXER1 implication in cancer progression and might be of value for the design of novel OXER1 antagonists.

• Authors: Konstantina Kalyvianaki, Irene Drosou, George Notas, Elias Castanas, Marilena Kampa
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 584 Pg. 95-100 (12 20 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 34775286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• 5-oxo-eicosatetraenoic acid
• Arachidonic Acids
• OXER1 protein, human
• Receptors, Eicosanoid

Topics

• Arachidonic Acids (metabolism, pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Cell Movement (drug effects, genetics)
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Humans
• Neoplasms (genetics, metabolism, pathology)
• Receptors, Eicosanoid (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects, genetics)
• Up-Regulation (drug effects)