ArticleCell reports2014
The oncogenic STP axis promotes triple-negative breast cancer via degradation of the REST tumor suppressor.
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Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Loss of negative regulation by HDAC1 and REST contributes to MAD1 overexpression in breast cancer.Molecular biology of the cell · 2025Article
- Small intestinal neuroendocrine tumors lack early genomic drivers, acquire DNA repair defects and harbor hallmarks of low REST expression.Scientific reports · 2025Article
- REST Is Restless in Neuronal and Non-Neuronal Virus Infections: An In Silico Analysis-Based Perspective.Viruses · 2025Review
- Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.International journal of molecular sciences · 2025Article
- PLK1 in cancer therapy: a comprehensive review of immunomodulatory mechanisms and therapeutic opportunities.Frontiers in immunology · 2025Review
- Distinct Transcriptomic and Tumor Microenvironment Profiles in Sinonasal Mucosal Melanoma and Aggressive Cutaneous Melanomas.Cancers · 2024Article
- SCYL1-mediated regulation of the mTORC1 signaling pathway inhibits autophagy and promotes gastric cancer metastasis.Journal of cancer research and clinical oncology · 2024Article
- Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling.Cell reports. Medicine · 2024Article
- A novel bioinformatic approach reveals cooperation between Cancer/Testis genes in basal-like breast tumors.Oncogene · 2024Article
- The Role of Polo-Like Kinase 1 in Regulating the Forkhead Box Family Transcription Factors.Cells · 2023Review
- Overexpression of SCYL1 Is Associated with Progression of Breast Cancer.Current oncology (Toronto, Ont.) · 2022Article
- mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1.Nature communications · 2022Article
- High-Resolution Bisulfite-Sequencing of Peripheral Blood DNA Methylation in Early-Onset and Familial Risk Breast Cancer Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Review
- Identification of Key Genes and Pathways Associated with RUNX1 Mutations in Acute Myeloid Leukemia Using Bioinformatics Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Overlapping Role of SCYL1 and SCYL3 in Maintaining Motor Neuron Viability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Chromosome 19 miRNA cluster and CEBPB expression specifically mark and potentially drive triple negative breast cancers.PloS one · 2018Article
- Hyperactive mTOR and MNK1 phosphorylation of eIF4E confer tamoxifen resistance and estrogen independence through selective mRNA translation reprogramming.Genes & development · 2017Article
- The Emerging Role of Polo-Like Kinase 1 in Epithelial-Mesenchymal Transition and Tumor Metastasis.Cancers · 2017Review
- FBP1 expression is associated with basal-like breast carcinoma.Oncology letters · 2017Article
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Authors and funding
25 authors at 4 institutions in 1 country.
Kristen L KarlinVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Integrative Molecular and Biomedical Sciences Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Gourish MondalDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Jessica K HartmanVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Siddhartha TyagiVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Sarah J KurleyVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Chris S BlandVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Tiffany Y T HsuVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Integrative Molecular and Biomedical Sciences Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Alexander RenwickDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Justin E FangVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Ilenia MigliaccioThe Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Celetta CallawayDepartment of Molecular and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Amritha NairVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Rocio Dominguez-VidanaVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Integrative Molecular and Biomedical Sciences Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Don X NguyenDepartment of Pathology, Yale University School of Medicine, Yale Cancer Center, New Haven, CT 06510, USA.
C Kent OsborneThe Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Rachel SchiffThe Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Li-Yuan Yu-LeeDepartment of Molecular and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Sung Y JungVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dean P EdwardsDepartment of Molecular and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Susan G HilsenbeckDan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jeffrey M RosenDepartment of Molecular and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Xiang H-F ZhangDepartment of Molecular and Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; The Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Chad A ShawDepartment of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Thomas F WestbrookVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Integrative Molecular and Biomedical Sciences Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: thomasw@bcm.edu.
Baylor College of Medicine · USMayo Clinic · USWinnMed · USYale University · US
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9MThe Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2005 to 2026
$49.9MMALAT1 lncRNA as a Therapeutic Target in Triple Negative Breast CancerR01CA016303 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ROSEN, JEFFREY MARK · 1985 to 2022
$8.1MTRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM008231 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI NELSON, DAVID LOREN · 1990 to 2019
$7.2MBRCA2 missense mutations and breast cancerR01CA116167 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2007 to 2011
$3.0MBRCA1 and BRCA2 missense mutations and breast cancer riskU01CA116167 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2013 to 2017
$2.7MDiscovering genetic networks of triple-negative breast cancerR01CA178039 · NCI · BAYLOR COLLEGE OF MEDICINE · PI WESTBROOK, THOMAS · 2013 to 2017
$1.6MElucidating the functions of Bud31, an essential gene in Myc-driven breast cancerF30CA180447 · NCI · BAYLOR COLLEGE OF MEDICINE · PI HSU, TIFFANY Y · 2013 to 2016
$156kNCI NIH HHS 1R01CA178039-01NCI NIH HHS CA116167NCI NIH HHS F30 CA180447NCI NIH HHS P30 CA125123NCI NIH HHS P30CA125123NCI NIH HHS P50 CA116201NCI NIH HHS P50 CA166201NCI NIH HHS R01 CA116167NCI NIH HHS R01 CA178039NCI NIH HHS U01 CA116167NIGMS NIH HHS 5 T32 GM008231NIGMS NIH HHS T32 GM008231
Abstract
Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, the aggressive triple-negative breast cancer subtype (TNBC) remains recalcitrant to targeted therapies because its molecular etiology is poorly defined. In this study, we used a forward genetic screen to discover an oncogenic network driving human TNBC. SCYL1, TEX14, and PLK1 ("STP axis") cooperatively trigger degradation of the REST tumor suppressor protein, a frequent event in human TNBC. The STP axis induces REST degradation by phosphorylating a conserved REST phospho-degron and bridging REST interaction with the ubiquitin-ligase βTRCP. Inhibition of the STP axis leads to increased REST protein levels and impairs TNBC transformation, tumor progression, and metastasis. Expression of the STP axis correlates with low REST protein levels in human TNBCs and poor clinical outcome for TNBC patients. Our findings demonstrate that the STP-REST axis is a molecular driver of human TNBC.
Indexed as
Signal TransductionAnimalsCarcinogenesisCell Cycle ProteinsCell Line, TumorCell Transformation, NeoplasticFemaleGene AmplificationHumansMiceNeoplasm MetastasisPhosphorylationPolo-Like Kinase 1Protein Serine-Threonine KinasesProteolysisProto-Oncogene ProteinsCell Cycle ProteinsPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsRE1-Silencing Transcription FactorRepressor Proteins
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