ArticleCancer research2016
Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
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- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- TIF1 Family Proteins as Modulators of Cell Death: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- Mitochondrial oxidative stress under hypoxia promotes gastric mucosal injury in portal hypertensive gastropathy.Biomedical reports · 2026Article
- Identification of a lipid oxygen radical defense pathway and its epigenetic control.Nature communications · 2025Article
- ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer.Molecular therapy. Oncology · 2025Review
- Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway.Journal for immunotherapy of cancer · 2025Article
- ZMAT2 condensates regulate the alternative splicing of TRIM28 to reduce cellular ROS accumulation, thereby promoting the proliferation of HCC cells.Cell communication and signaling : CCS · 2024Article
- Review
- Disarib, a Specific BCL2 Inhibitor, Induces Apoptosis in Triple-Negative Breast Cancer Cells and Impedes Tumour Progression in Xenografts by Altering Mitochondria-Associated Processes.International journal of molecular sciences · 2024Article
- Mitochondrial dysfunction induced by HIF-1α under hypoxia contributes to the development of gastric mucosal lesions.Clinical and translational medicine · 2024Article
- TRIM28 in cancer and cancer therapy.Frontiers in genetics · 2024Review
- Inhibition of Drp1 orchestrates the responsiveness of breast cancer cells to paclitaxel but insignificantly relieves paclitaxel-related ovarian damage in mice.Scientific reports · 2023Article
- The role of mitochondrial dynamics in disease.MedComm · 2023Review
- Mitochondrial structure and function adaptation in residual triple negative breast cancer cells surviving chemotherapy treatment.Oncogene · 2023Article
- Autophagy/Mitophagy Regulated by Ubiquitination: A Promising Pathway in Cancer Therapeutics.Cancers · 2023Review
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
- AMPK/MFF Activation: Role in Mitochondrial Fission and Mitophagy in Dry Eye.Investigative ophthalmology & visual science · 2022Article
- Mitochondrial dynamics regulators: implications for therapeutic intervention in cancer.Cell biology and toxicology · 2022Review
- Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner. Mechanistic investigations using phosphorylation-defective mutants revealed that KAP1 Ser473 phosphorylation limited mitochondrial hyperfusion in glucose-starved breast cancer cells, as driven by downregulation of the mitofusin protein MFN2, leading to reduced oxidative phosphorylation and ROS production. In clinical specimens of breast cancer, reduced expression of MFN2 corresponded to poor prognosis in patients. In a mouse xenograft model of human breast cancer, there was an association in the core region of tumors between MFN2 downregulation and the presence of highly fragmented mitochondria. Collectively, our results suggest that KAP1 Ser473 phosphorylation acts through MFN2 reduction to restrict mitochondrial hyperfusion, thereby contributing to cancer cell survival under conditions of sustained metabolic stress. Cancer Res; 76(17); 5006-18. ©2016 AACR.
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