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Enhanced OXER1 expression is indispensable for human cancer cell migration
Konstantina Kalyvianaki1, Irene Drosou1, George Notas1
1Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, Greece.
Biochemical and Biophysical Research Communications
|November 14, 2021
Summary
The OXER1 receptor and its ligand 5-oxo-ETE play a crucial role in cancer cell migration, mimicking wound healing processes. Inhibiting OXER1 or 5-oxo-ETE reduces cancer cell movement and prolongs healing.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- OXER1 is an inflammatory receptor binding 5-oxo-ETE, involved in cell chemoattraction, inflammation, and cancer.
- OXER1 also functions as a membrane androgen receptor in cancer tissues.
- Wounded tissues release 5-oxo-ETE, attracting lymphocytes, a process similar to cancer hallmarks.
Purpose of the Study:
- To explore the role of OXER1 and 5-oxo-ETE in human cancer epithelial cell migration.
- To investigate OXER1's function in mimicking the activation/migration phase of wound healing in cancer cells.
Main Methods:
- Studied human cancer epithelial cell lines (DU-145, T47D, Hep3B).
- Examined OXER1 expression and its regulation by 5-oxo-ETE.
- Utilized OXER1 knock-down and 5-oxo-ETE synthesis inhibition.
- Analyzed changes in cell migration, actin cytoskeleton, and filopodia formation.
- Investigated the role of Gβγ signaling in OXER1-mediated effects.
Main Results:
- OXER1 is upregulated at the leading edge of migrating cancer cells and induced by 5-oxo-ETE.
- Knock-down of OXER1 or inhibition of 5-oxo-ETE significantly decreased cancer cell migration.
- Reduced cell migration was associated with actin cytoskeleton modification and decreased filopodia.
- Cell migration inhibition is mediated by Gβγ OXER1-dependent pathways.
Conclusions:
- OXER1 and 5-oxo-ETE are key players in cancer cell migration, analogous to wound healing.
- These findings reveal a novel mechanism for OXER1's role in cancer progression.
- OXER1 antagonists could be valuable for developing new cancer therapies.
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