Maria Babak, Head of The Babak Lab and Assistant Professor at City University of Hong Kong, shared The Babak Lab’s post on LinkedIn, adding:
“The link between palmitoylation and epigenetic regulation is particularly interesting.”
Quoting The Babak Lab’s post on LinkedIn:
“Scientific Wednesdays: Palmitoylation controls KAT2A expression in breast cancer metastasis
A new study in Nature Cell Biology identifies a lipid modification pathway that regulates a key epigenetic enzyme in metastatic breast cancer.
Key Focus
The study investigates how expression of the acetyltransferase KAT2A is controlled in breast cancer metastases and links this regulation to protein palmitoylation.
Key Insights
- The palmitoyltransferase ZDHHC20 modifies TM4SF1, promoting its localization to the plasma membrane.
- This activates STAT3 phosphorylation, which functions as a transcriptional regulator of KAT2A.
- Silencing ZDHHC20 or TM4SF1, or disrupting TM4SF1 palmitoylation, significantly reduced lung metastasis growth.
- Restoration of KAT2A expression rescued metastatic growth, confirming its functional role downstream of this pathway.
- Evidence of this signaling axis was observed in lung metastasis samples from patients with breast cancer.
Mechanism
Palmitoylation of TM4SF1 by ZDHHC20 enhances membrane signaling, leading to STAT3 activation and transcriptional upregulation of KAT2A, a global regulator of acetylation.
Conclusion
This work uncovers a link between lipid modification and epigenetic regulation in metastasis, suggesting that targeting palmitoylation or the ZDHHC20–TM4SF1–STAT3 axis may provide new strategies to control metastatic disease.
Image generated using Sora by OpenAI.
Title: Palmitoylation-mediated regulation of KAT2A promotes lung metastasis in breast cancer
Authores: Ming Liu, Anke Vandekeere, Xiao-Zheng Liu, Stephan Schenck, Juan Fernández-García, Tine Tricot Yiming Peng-Winkler, Margherita Demicco, Dorien Broekaert, Ines Vermeire, Janine Theile, Gitte Zels, Anirudh Pabba, Christine Desmedt, Janine D. Brunner, Patricia Altea-Manzano, Sarah-Maria Fendt.”
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