ArticleScience (New York, N.Y.)2024
A p62-dependent rheostat dictates micronuclei catastrophe and chromosome rearrangements.
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Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31citing papers in PubMed
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Who cites it
31 citing papers in PubMed.
- The role of cytosolic mitochondrial DNA as a mitochondrial danger signal for stromal fibroblasts in forming the tumor-promoting microenvironment following radiation exposure.Journal of radiation research · 2026Review
- Unraveling the lexicon of complex mutational phenomena in human cancers.Nature cancer · 2026Review
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.Molecular cancer · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- BAP1 deficiency-induced SKA3 promotes clear cell renal cell carcinoma malignant progression by regulating chromosomal instability.Cell death & disease · 2026Article
- Chromosomal Instability Drives Glioblastoma Heterogeneity and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Getting nuclear size just right - emerging mechanisms regulating nuclear scaling and morphology.Journal of cell science · 2026Review
- Autophagy is essential for survival and function of polyploid giant cancer cells under therapeutic stress.Cancer letters · 2026Article
- ESCRT-III function in membrane fission and repair.Nature reviews. Molecular cell biology · 2026Review
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Micronuclei: origins, assays, mechanisms, diseases and treatments.Signal transduction and targeted therapy · 2026Review
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- Mitotic errors as triggers of cell death and inflammation.Nature cell biology · 2026Review
- LRRC59 cooperates with nuclear transporters to restrain the nuclear envelope repair machinery and safeguard genome integrity.Nature communications · 2025Article
- Comprehensive pan-cancer analysis of p62 reveals its contribution to shaping tumor microenvironment and anti-tumor immunity.Discover oncology · 2025Article
- Nuclear and genome dynamics underlying DNA double-strand break repair.Nature reviews. Molecular cell biology · 2025Review
- Aneuploidy-induced proteostasis disruption impairs mitochondrial functions and mediates aggregation of mitochondrial precursor proteins through SQSTM1/p62.Nature communications · 2025Article
- Review
- Cancer cells' chamber of secrets: the link between micronuclei, chromothripsis and malignancy.Open biology · 2025Review
Corrections and comments
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Authors and funding
29 authors.
Sara MartinDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.ORCID 0009-0003-7289-2028
Simone ScorzoniDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.ORCID 0000-0003-2046-2678
Sara CordoneDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.
Alice MazzagattiDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1627-0446
Galina V BeznoussenkoIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Amanda L GunnDivision of Basic Sciences and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0002-9450-4976
Melody Di BonaHuman Oncology and Pathogenesis Program and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-8853-2604
Yonatan EliezerDepartment of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID 0009-0002-0515-7579
Gil LeorDepartment of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID 0000-0003-2225-5744
Tal Ben-YishayDepartment of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID 0009-0005-1305-0001
Alessia LoffredaExperimental Imaging Center, IRCCS Ospedale San Raffaele, Milan, Italy.ORCID 0000-0003-4523-5666
Valeria CancilaTumor Immunology Unit, Department of Sciences for Health Promotion and Mother-Child Care "G. D'Alessandro," University of Palermo, Palermo, Italy.
Maria Chiara RainoneDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.
Marica Rosaria IppolitoDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.ORCID 0000-0001-7310-1871
Valentino MartisDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.
Fabio BedinDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.ORCID 0009-0006-4313-7762
Massimiliano GarrèIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.ORCID 0000-0001-9332-0270
Laura Pontano VaitesDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Paolo VasapolliDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.ORCID 0009-0007-8678-5951
Simona PoloIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.ORCID 0000-0001-5536-9399
Dario ParazzoliIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.ORCID 0000-0001-8176-9775
Claudio TripodoIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.ORCID 0000-0002-0821-6231
Alexander A MironovIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Alessandro CuomoDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.ORCID 0000-0002-9778-7190
Uri Ben-DavidDepartment of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID 0000-0001-7098-2378
Samuel F BakhoumHuman Oncology and Pathogenesis Program and Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-0295-3564
Emily M HatchDivision of Basic Sciences and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0002-3393-4075
Peter LyDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-8946-7069
Stefano SantaguidaDepartment of Experimental Oncology at IEO, European Institute of Oncology IRCCS, Milan, Italy.ORCID 0000-0002-1501-6190
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTranslational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MTargeting Polθ to Overcome PARP Inhibitor Resistance in Homologous Recombination Deficient Breast CancerP50CA247749 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Simon N. Powell · 2020 to 2026
$16.3MProbing cytosolic nucleic acid sensing pathways in cancerR01CA256188 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LAUGHNEY, ASHLEY MARIE · 2021 to 2025
$3.5MDissecting the impact of tumor-intrinsic chromosomal instability on the cancer ecosystemR01CA280572 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN BLENIS, Ashley Marie Laughney · 2023 to 2026
$2.9MMulti-cellular interactions defining the human brain metastatic nicheR01CA280414 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar, Ashley Marie Laughney · 2023 to 2026
$2.8MThe role of chromosomal instability in tumor evolutionDP5OD026395 · OD · SLOAN-KETTERING INST CAN RESEARCH · PI BAKHOUM, SAMUEL F · 2018 to 2022
$2.2MMechanisms regulating nuclear envelope structure and stabilityR35GM124766 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HATCH, EMILY M · 2017 to 2021
$2.2MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015704NCI NIH HHS P50 CA247749NCI NIH HHS R01 CA256188NCI NIH HHS R01 CA280414NCI NIH HHS R01 CA280572NIGMS NIH HHS R35 GM124766NIH HHS DP5 OD026395
Abstract
Chromosomal instability (CIN) generates micronuclei-aberrant extranuclear structures that catalyze the acquisition of complex chromosomal rearrangements present in cancer. Micronuclei are characterized by persistent DNA damage and catastrophic nuclear envelope collapse, which exposes DNA to the cytoplasm. We found that the autophagic receptor p62/SQSTM1 modulates micronuclear stability, influencing chromosome fragmentation and rearrangements. Mechanistically, proximity of micronuclei to mitochondria led to oxidation-driven homo-oligomerization of p62, limiting endosomal sorting complex required for transport (ESCRT)-dependent micronuclear envelope repair by triggering autophagic degradation. We also found that p62 levels correlate with increased chromothripsis across human cancer cell lines and with increased CIN in colorectal tumors. Thus, p62 acts as a regulator of micronuclei and may serve as a prognostic marker for tumors with high CIN.
Indexed as
AutophagyChromosomal InstabilityChromothripsisColorectal NeoplasmsMicronuclei, Chromosome-DefectiveSequestosome-1 ProteinCell Line, TumorDNA DamageEndosomal Sorting Complexes Required for TransportHumansMitochondriaNuclear EnvelopeEndosomal Sorting Complexes Required for TransportSequestosome-1 ProteinSQSTM1 protein, human
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