{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:22:07Z","timestamp":1791915727937,"version":"4.3.4"},"reference-count":34,"publisher":"American Association for Cancer Research (AACR)","issue":"8","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Macroautophagy (autophagy hereafter) recycles intracellular components to sustain mitochondrial metabolism that promotes the growth, stress tolerance, and malignancy of lung cancers, suggesting that autophagy inhibition may have antitumor activity. To assess the functional significance of autophagy in both normal and tumor tissue, we conditionally deleted the essential autophagy gene, autophagy related 7 (Atg7), throughout adult mice. Here, we report that systemic ATG7 ablation caused susceptibility to infection and neurodegeneration that limited survival to 2 to 3 months. Moreover, upon fasting, autophagy-deficient mice suffered fatal hypoglycemia. Prior autophagy ablation did not alter the efficiency of non\u2013small cell lung cancer (NSCLC) initiation by activation of oncogenic KrasG12D and deletion of the Trp53 tumor suppressor. Acute autophagy ablation in mice with preexisting NSCLC, however, blocked tumor growth, promoted tumor cell death, and generated more benign disease (oncocytomas). This antitumor activity occurred before destruction of normal tissues, suggesting that acute autophagy inhibition may be therapeutically beneficial in cancer.<\/jats:p>\n                  <jats:p>Significance: We systemically ablated cellular self-cannibalization by autophagy in adult mice and determined that it is dispensable for short-term survival, but required to prevent fatal hypoglycemia and cachexia during fasting, delineating a new role for autophagy in metabolism. Importantly, acute, systemic autophagy ablation was selectively destructive to established tumors compared with normal tissues, thereby providing the preclinical evidence that strategies to inhibit autophagy may be therapeutically advantageous for RAS-driven cancers. Cancer Discov; 4(8); 914\u201327. \u00a92014 AACR.<\/jats:p>\n                  <jats:p>See related commentary by Amaravadi and Debnath, p. 873<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 855<\/jats:p>","DOI":"10.1158\/2159-8290.cd-14-0363","type":"journal-article","created":{"date-parts":[[2014,5,29]],"date-time":"2014-05-29T23:55:00Z","timestamp":1401407700000},"page":"914-927","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":528,"title":["Autophagy Is Required for Glucose Homeostasis and Lung Tumor Maintenance"],"prefix":"10.1158","volume":"4","author":[{"given":"Gizem","family":"Karsli-Uzunbas","sequence":"first","affiliation":[{"name":"1Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey."},{"name":"2Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New 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Jersey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinan","family":"Khor","sequence":"additional","affiliation":[{"name":"1Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey."},{"name":"2Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada Y.","family":"Kalaany","sequence":"additional","affiliation":[{"name":"4Division of Endocrinology, Center for Basic and Translational Obesity Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Jacks","sequence":"additional","affiliation":[{"name":"5Koch Institute for Integrative Cancer Research and Department of Biology, MIT, Cambridge, Massachusetts."},{"name":"6Howard Hughes Medical Institute, MIT, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang S.","family":"Chan","sequence":"additional","affiliation":[{"name":"1Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey."},{"name":"7Deparment of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Rabinowitz","sequence":"additional","affiliation":[{"name":"1Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey."},{"name":"3Department of Chemistry, Princeton University, Princeton, New Jersey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"White","sequence":"additional","affiliation":[{"name":"1Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey."},{"name":"2Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New 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