NONO interacts with nuclear PKM2 and directs histone H3 phosphorylation to promote triple-negative breast cancer metastasis
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View abstract on PubMed
Summary
This summary is machine-generated.Nuclear PKM2 interacts with NONO to promote triple-negative breast cancer (TNBC) metastasis by phosphorylating histone H3. This epigenetic regulation of SERPINE1 offers a new therapeutic target for TNBC.
Area Of Science
- Molecular Oncology
- Epigenetics
- Cancer Biology
Background
- Pyruvate kinase M2 (PKM2) exhibits oncogenic functions beyond its enzymatic activity, acting as a protein kinase regulating gene expression.
- The precise mechanisms by which PKM2, as a histone kinase, influences gene transcription in triple-negative breast cancer (TNBC) metastasis are not fully understood.
Purpose Of The Study
- To investigate the epigenetic regulation of TNBC metastasis mediated by nuclear PKM2 through its interaction with NONO.
- To elucidate the role of PKM2-dependent histone modifications in promoting TNBC cell proliferation, migration, and invasion.
Main Methods
- Integrated cellular, biochemical, and molecular analyses, including ChIP, RNA-Seq, and mouse models.
- Investigated protein-protein interactions between NONO and nuclear PKM2.
- Analyzed histone modifications (H3T11ph, H3K27ac) and their impact on gene expression (SERPINE1).
Main Results
- Identified direct interaction between transcription factor NONO and nuclear PKM2.
- Demonstrated that NONO directs PKM2-mediated H3T11ph, which cooperates with H3K27ac to activate SERPINE1 expression.
- Showed that loss of NONO or PKM2 suppresses SERPINE1, attenuates tumor progression in mice, and correlates with poor outcomes in TNBC patients.
Conclusions
- The NONO-dependent interaction with nuclear PKM2 is crucial for the epigenetic modulation of TNBC metastasis.
- This pathway represents a novel therapeutic strategy for TNBC treatment.
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