title: Down-regulation of autophagy-related protein 5 (ATG5) contributes to the pathogenesis of early-stage cutaneous melanoma.
abstract: The role of autophagy in cancer is controversial: Both tumor-suppressing and tumor-promoting functions have been reported. We show that a key regulator of autophagy, autophagy-related protein 5 (ATG5), is often down-regulated in primary melanomas compared to benign nevi, leading to a reduction of basal autophagy as evidenced by a reduced expression of LC3. A follow-up of 158 primary melanoma patients showed that patients with low levels of ATG5 in their tumors had a reduced progression-free survival. In an in vitro model of melanoma tumorigenesis, where the BRAF oncogene was transduced into normal melanocytes, we observed that lowering ATG5 expression promoted proliferation by precluding oncogene-induced senescence. Hence, it appears that down-regulation of ATG5 contributes to tumorigenesis in early-stage cutaneous melanoma, and the expression of ATG5 and LC3 correlates with melanoma diagnosis and prognosis.
authors.affiliation: Institute of Pharmacology, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: He
authors.forename: Thomas
authors.initials: T
authors.lastname: von Rütte
authors.forename: Shida
authors.initials: S
authors.lastname: Yousefi
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hunger
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
mesh_terms: D001343:Autophagy / Q000235:genetics; D000071187:Autophagy-Related Protein 5; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D006801:Humans; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008954:Models, Biological; D009367:Neoplasm Staging; D009508:Nevus, Pigmented / Q000235:genetics / Q000473:pathology; D009857:Oncogenes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins