Autophagy suppresses tumor progression by limiting chromosomal instability. 2007

Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

Autophagy is a bulk degradation process that promotes survival under metabolic stress, but it can also be a means of cell death if executed to completion. Monoallelic loss of the essential autophagy gene beclin1 causes susceptibility to metabolic stress, but also promotes tumorigenesis. This raises the paradox that the loss of a survival pathway enhances tumor growth, where the exact mechanism is not known. Here, we show that compromised autophagy promoted chromosome instability. Failure to sustain metabolism through autophagy was associated with increased DNA damage, gene amplification, and aneuploidy, and this genomic instability may promote tumorigenesis. Thus, autophagy maintains metabolism and survival during metabolic stress that serves to protect the genome, providing an explanation for how the loss of a survival pathway leads to tumor progression. Identification of this novel role of autophagy may be important for rational chemotherapy and therapeutic exploitation of autophagy inducers as potential chemopreventive agents.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008660 Metabolism The chemical reactions in living organisms by which energy is provided for vital processes and activities and new material is assimilated. Anabolism,Catabolism,Metabolic Concepts,Metabolic Phenomena,Metabolic Processes,Metabolic Phenomenon,Metabolic Process,Metabolism Concepts,Metabolism Phenomena,Process, Metabolic,Processes, Metabolic,Concept, Metabolic,Concept, Metabolism,Concepts, Metabolic,Concepts, Metabolism,Metabolic Concept,Metabolism Concept,Phenomena, Metabolic,Phenomena, Metabolism,Phenomenon, Metabolic
D008869 Microtubule-Associated Proteins High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules. Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D010746 Phosphonoacetic Acid A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent. Phosphonoacetate,Disodium Phosphonoacetate,Fosfonet Sodium,Phosphonacetic Acid,Phosphonoacetate, Disodium
D011003 Ploidies The degree of replication of the chromosome set in the karyotype. Ploidy
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality

Related Publications

Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
August 2018, Nature communications,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
October 2015, Cancer research,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
January 2023, Journal of oncology,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
September 2001, Molecular and cellular biology,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
November 2023, International journal of molecular sciences,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
September 2017, Endocrine-related cancer,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
May 2023, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
July 2021, Developmental cell,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
September 2016, Oncotarget,
Robin Mathew, and Sameera Kongara, and Brian Beaudoin, and Cristina M Karp, and Kevin Bray, and Kurt Degenhardt, and Guanghua Chen, and Shengkan Jin, and Eileen White
May 2016, Scientific reports,
Copied contents to your clipboard!