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Published on: February 4, 2021
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Microglial TBK1 Signaling Promotes Breast Cancer Brain Metastasis
Fatima Khan1,2, Edgar Petrosyan2, Yang Liu1,2
1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Cancer Research
|September 18, 2025
Summary
Targeting TANK-binding kinase 1 (TBK1) in tumor-associated microglia may treat breast cancer brain metastasis. Inhibiting TBK1 reduces cancer cell growth and migration, offering a new therapeutic strategy.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Breast cancer brain metastasis (BCBM) is a lethal complication.
- Tumor-associated microglia (TAMG) promote BCBM progression.
- Understanding TAMG mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of TANK-binding kinase 1 (TBK1) signaling in TAMG.
- To identify molecular mechanisms by which TAMG promote BCBM.
- To evaluate TBK1 inhibition as a therapeutic strategy for BCBM.
Main Methods:
- Analysis of human BCBM samples and mouse models.
- In vitro microglia culture systems.
- Transcriptomic profiling, secretome analysis, and survival data analysis.
- Pharmacologic inhibition of TBK1.
Main Results:
- TBK1 signaling is enriched and activated in TAMG from BCBM.
- TBK1 inhibition in TAMG suppressed breast cancer cell epithelial-mesenchymal transition, migration, invasion, and proliferation.
- GM-CSF was identified as a key mediator of TBK1-regulated breast cancer cell metastasis.
- Pharmacologic TBK1 inhibition reduced BCBM and improved survival in mouse models.
Conclusions:
- TBK1 signaling in TAMG drives BCBM progression.
- TBK1 and its downstream effector GM-CSF are promising therapeutic targets for BCBM.
- Targeting TBK1 in TAMG offers a potential strategy to treat breast cancer brain metastasis.
