title: Chaperone-mediated autophagy is required for tumor growth.
abstract: The cellular process of autophagy (literally "self-eating") is important for maintaining the homeostasis and bioenergetics of mammalian cells. Two of the best-studied mechanisms of autophagy are macroautophagy and chaperone-mediated autophagy (CMA). Changes in macroautophagy activity have been described in cancer cells and in solid tumors, and inhibition of macroautophagy promotes tumorigenesis. Because normal cells respond to inhibition of macroautophagy by up-regulation of the CMA pathway, we aimed to characterize the CMA status in different cancer cells and to determine the contribution of changes in CMA to tumorigenesis. Here, we show consistent up-regulation of CMA in different types of cancer cells regardless of the status of macroautophagy. We also demonstrate an increase in CMA components in human cancers of different types and origins. CMA is required for cancer cell proliferation in vitro because it contributes to the maintenance of the metabolic alterations characteristic of malignant cells. Using human lung cancer xenografts in mice, we confirmed the CMA dependence of cancer cells in vivo. Inhibition of CMA delays xenograft tumor growth, reduces the number of cancer metastases, and induces regression of existing human lung cancer xenografts in mice. The fact that similar manipulations of CMA also reduce tumor growth of two different melanoma cell lines suggests that targeting this autophagic pathway may have broad antitumorigenic potential.
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Kon
authors.forename: Roberta
authors.initials: R
authors.lastname: Kiffin
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koga
authors.forename: Javier
authors.initials: J
authors.lastname: Chapochnick
authors.forename: Fernando
authors.initials: F
authors.lastname: Macian
authors.forename: Lyuba
authors.initials: L
authors.lastname: Varticovski
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D018832:Molecular Chaperones; D034741:RNA, Small Interfering
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