Abstract
Autophagy--a process of "self-eating" that involves enzymatic digestion and recycling of cellular constituents in response to stress--contributes to both cancer cell death and survival. In this issue of the JCI, Lu et al. report that controlled induction of tumor suppressor gene aplasia Ras homolog member I (ARHI) results in autophagic cell death of human ovarian cancer cells in vitro (see the related article beginning on page 3917). However, within xenograft tumors in mice, multiple factors within the tumor microenvironment switched ARHI-induced autophagy to a mechanism of tumor cell survival, leading to tumor dormancy. Since ARHI expression is suppressed in the majority of breast and ovarian cancers but is high in premalignant lesions, ARHI-induced autophagy could be manipulated for therapeutic benefit.
Publication types
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Research Support, N.I.H., Extramural
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Comment
MeSH terms
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Animals
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Antibiotics, Antineoplastic / pharmacology
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Antirheumatic Agents / pharmacology
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Autophagy / drug effects
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Autophagy / genetics
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Cell Line, Tumor
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Cell Survival / drug effects
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Cell Survival / genetics
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Chloroquine / pharmacology
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism
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Female
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Genomic Imprinting / drug effects
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Genomic Imprinting / genetics
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Humans
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Intercellular Signaling Peptides and Proteins / pharmacology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Neoplasm Transplantation
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism*
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Ovarian Neoplasms / pathology
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Phagosomes / genetics
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Phagosomes / metabolism
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Sirolimus / pharmacology
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TOR Serine-Threonine Kinases
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Transplantation, Heterologous
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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rho GTP-Binding Proteins / genetics
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rho GTP-Binding Proteins / metabolism*
Substances
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Antibiotics, Antineoplastic
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Antirheumatic Agents
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DIRAS3 protein, human
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Intercellular Signaling Peptides and Proteins
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MAP1LC3A protein, human
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Microtubule-Associated Proteins
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Tumor Suppressor Proteins
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Chloroquine
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Protein Kinases
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MTOR protein, human
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mTOR protein, mouse
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TOR Serine-Threonine Kinases
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Cysteine Endopeptidases
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rho GTP-Binding Proteins
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Sirolimus