ArticleCell reports2023
5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling.
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Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 40 citations in OpenAlex.
- Metabolites and cancer metastasis.Oncogene · 2026Review
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers.Journal of experimental & clinical cancer research : CR · 2026Article
- Dormancy exit correlates with CREB1 reactivation that is a potential target to overcome endocrine therapy resistance in ERiScience · 2026Article
- Ubiquitination of DDX21 by HERC2 induces a dormancy-like phenotype via the NUCKS1-p21/p27 axis to promote radio-resistance in colorectal cancer cells.Cell death & disease · 2026Article
- Targeting the CCL5/CCR5-PI3K-AKT axis suppresses hepatic stellate cell-induced breast cancer metastasis.Cancer cell international · 2026Article
- Metastasis on pause: How dormant tumor cells stay hidden within the tumor microenvironment and evade immune surveillance.Molecular oncology · 2026Review
- Targeting dormant cancer cells: ferroptosis as a precision therapeutic strategy.Cellular & molecular biology letters · 2026Review
- Drug-Tolerant Persister Cells and Tumor Dormancy in NSCLC: A New Frontier in Overcoming Therapeutic Resistance.Cancers · 2026Review
- TGFβ induces an atypical EMT to evade immune mechanosurveillance in lung adenocarcinoma dormant metastasis.Nature cancer · 2026Article
- Decoding cancer dormancy: integrative genomic, phenotypic and live-cell imaging analysis to reveal the hidden cancer cell reservoir.Molecular cancer · 2025Review
- Cancer Cell Dormancy in the Bone Microenvironment.Current osteoporosis reports · 2025Review
- Review
- Review
- A Pilot Study of the Combination of 5-Azacitidine and All-trans Retinoic Acid in Biochemically Recurrent Prostate Cancer.medRxiv : the preprint server for health sciences · 2025Article
- Macrophage regulation of tumor cell dormancy and the dormant niche: an overview in solid tumors.Cancer metastasis reviews · 2025Review
- Diagnosis and therapeutic targeting of quiescent cancer cells: road to conquer cancer recurrence.BMB reports · 2025Review
- Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Enter sandman: how to tackle dormant breast cancer cells.Medical oncology (Northwood, London, England) · 2025Review
- Lung-specific metastasis: the coevolution of tumor cells and lung microenvironment.Molecular cancer · 2025Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Deepak K SinghDivision of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Cancer Dormancy and Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, NY, USA.
Saul CarcamoDepartment of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Bioinformatics for Next Generation Sequencing Facility, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eduardo F FariasDivision of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Dan HassonDepartment of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Bioinformatics for Next Generation Sequencing Facility, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Wei ZhengDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Cancer Dormancy and Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, NY, USA.
Dan SunDivision of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Cancer Dormancy and Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, NY, USA.
Xin HuangDepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Cancer Dormancy and Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, NY, USA.
Julie CheungDivision of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ana Rita NobreDivision of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nupura KaleDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Maria Soledad SosaDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Emily BernsteinDepartment of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Julio A Aguirre-GhisoDivision of Hematology and Oncology, Department of Medicine and Department of Otolaryngology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Cancer Dormancy and Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, NY, USA; Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, USA; Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: julio.aguirre-ghiso@einsteinmed.edu.
Icahn School of Medicine at Mount Sinai · USAlbert Einstein College of Medicine · US
Funding
WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2MTHE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4MFunctional Determinants of Metastatic DormancyR01CA109182 · NCI · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI AGUIRRE-GHISO, JULIO A. · 2005 to 2025
$8.3MDeciphering the tumor suppressive functions of macroH2AR01CA154683 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BERNSTEIN, EMILY · 2011 to 2021
$3.9M(7) Novel imaging devices for measurement and control of tumor microenvironmentsR01CA216248 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CADY, NATHANIEL CHARLES, CONDEELIS, JOHN S · 2017 to 2021
$2.9MEpigenetic and microenvironmental regulation of dormant disseminated cancerR01CA218024 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AGUIRRE-GHISO, JULIO A. · 2017 to 2021
$2.2MBig Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0MFunctional Analysis of Distinct and Co-existing Transcriptional Programs Regulating Tumor DormancyR01CA266443 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI Maria Sosa · 2023 to 2026
$1.5MHigh Speed, High Resolution Slide Scanner for Research in Translational MedicineS10OD026852 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI CONDEELIS, JOHN S · 2022 to 2022
$472kMechanisms of quiescence and pluripotency in disseminated tumor cellsK22CA201054 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SOSA, MARIA · 2017 to 2019
$380kNCI NIH HHS K22 CA201054NCI NIH HHS P30 CA013330NCI NIH HHS P30 CA196521NCI NIH HHS R01 CA109182NCI NIH HHS R01 CA154683NCI NIH HHS R01 CA216248NCI NIH HHS R01 CA218024NCI NIH HHS R01 CA266443NIH HHS S10 OD026852NIH HHS S10 OD026880
Abstract
Disseminated cancer cells (DCCs) in secondary organs can remain dormant for years to decades before reactivating into overt metastasis. Microenvironmental signals leading to cancer cell chromatin remodeling and transcriptional reprogramming appear to control onset and escape from dormancy. Here, we reveal that the therapeutic combination of the DNA methylation inhibitor 5-azacytidine (AZA) and the retinoic acid receptor ligands all-trans retinoic acid (atRA) or AM80, an RARα-specific agonist, promotes stable dormancy in cancer cells. Treatment of head and neck squamous cell carcinoma (HNSCC) or breast cancer cells with AZA+atRA induces a SMAD2/3/4-dependent transcriptional program that restores transforming growth factor β (TGF-β)-signaling and anti-proliferative function. Significantly, either combination, AZA+atRA or AZA+AM80, strongly suppresses HNSCC lung metastasis formation by inducing and maintaining solitary DCCs in a SMAD4
Indexed as
Breast NeoplasmsSignal TransductionSmad4 ProteinSquamous Cell Carcinoma of Head and NeckTretinoinAzacitidineBenzoatesCell Line, TumorHead and Neck NeoplasmsHumansTetrahydronaphthalenesTransforming Growth Factor betaAzacitidineBenzoatesSmad4 ProteinSMAD4 protein, humantamibaroteneTetrahydronaphthalenesTransforming Growth Factor betaTretinoinCP: CancerCP: Cell biologydisseminated cancer celldormancyenhancersmetastasistranscriptional reprogramming
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