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CDK5RAP3 is a co-factor for the oncogenic transcription factor STAT3
Susana P Egusquiaguirre1, Suhu Liu1, Isidora Tošić1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215; Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.
Neoplasia (New York, N.Y.)
|November 26, 2019
Summary
CDK5RAP3 enhances STAT3 gene expression, promoting cancer cell proliferation and migration. Silencing CDK5RAP3 inhibits these STAT3-driven tumor phenotypes, offering a potential therapeutic strategy for STAT3-mediated cancers.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- Signal transducer and activator of transcription 3 (STAT3) is a transcription factor crucial for cell proliferation, survival, and self-renewal.
- Constitutive activation of STAT3 is implicated in numerous cancers, driving malignant cellular behavior.
- STAT3's function can be modulated by protein interactions, offering potential therapeutic targets.
Purpose of the Study:
- To identify novel modulators of STAT3 transcriptional function.
- To investigate the role of CDK5RAP3 in STAT3-mediated gene expression and cancer phenotypes.
- To explore CDK5RAP3 as a potential therapeutic target and biomarker in STAT3-driven cancers.
Main Methods:
- An RNA-interference based screen was employed to quantitatively measure STAT3 activity.
- CDK5RAP3's interaction with STAT3-regulated genomic loci was assessed.
- Expression correlation between CDK5RAP3, STAT3 signatures, and target genes was analyzed in primary human breast cancers.
Main Results:
- CDK5RAP3 was identified as an enhancer of STAT3-dependent gene expression.
- Silencing CDK5RAP3 reduced STAT3-mediated cancer cell phenotypes, including clonogenesis and migration.
- CDK5RAP3 binds to STAT3-regulated genomic loci in a STAT3-dependent manner.
- CDK5RAP3 expression correlates with STAT3 gene expression signatures in human breast cancers.
Conclusions:
- CDK5RAP3 is a novel modulator of STAT3 transcriptional function.
- CDK5RAP3 enhances STAT3-driven tumorigenic phenotypes.
- CDK5RAP3 represents a potential biomarker and therapeutic target for STAT3-mediated cancers.
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