Discover how the intricate dance of proteins within our cells, driven by the ZDHHC5 enzyme, can influence the aggressive transformation of brain cancer, shedding light on potential new avenues for treatment.
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ZDHHC5-mediated S-palmitoylation of FAK promotes its membrane localization and epithelial-mesenchymal transition in glioma.
Wang et al., Cell Commun Signal 2024
DOI: 10.1186/s12964-023-01366-z
What’s New: This study uncovers the significance of S-palmitoylation, a post-translational modification, in the activation and function of Focal Adhesion Kinase (FAK) in glioblastoma (GBM) cells. It identifies ZDHHC5 as the palmitoyl acyltransferase that catalyzes this modification at a specific site (C456) on FAK.
Importance: The research highlights a novel regulatory mechanism of FAK, providing insights into how its abnormal activation contributes to tumor progression and metastasis in GBM.
Contribution to Literature: The findings suggest that the ZDHHC5/FAK axis is a potential target for therapeutic intervention in GBM.
Results Summary:
– Inhibition of FAK palmitoylation caused its redistribution from the membrane to the cytoplasm and reduced its phosphorylation.
– ZDHHC5 was identified as the enzyme responsible for FAK’s S-palmitoylation at C456.
– Knockdown of ZDHHC5 resulted in loss of FAK S-palmitoylation and membrane localization, leading to impaired cell proliferation, invasion, and epithelial-mesenchymal transition (EMT).
– The study utilized assays such as acyl-PEG exchange (APE), metabolic incorporation, Cell Counting Kit-8 (CCK8), colony formation, and Transwell, as well as intracranial GBM xenograft models to support these findings.
Therapeutic Potential: The research suggests that targeting the ZDHHC5/FAK interaction could be a promising strategy for GBM treatment.