title: Autophagy suppresses melanoma tumorigenesis by inducing senescence.
abstract: Whether and how autophagy is involved in tumorigenesis is poorly understood. We approached this question by investigating a relatively large cohort of patients with mostly early primary melanoma for their expression of 2 markers for autophagy, the protein ATG5 (autophagy-related 5) and MAP1LC3B/LC3 (microtubule-associated protein 1 light chain 3B). Surprisingly, we discovered that both ATG5 and LC3 levels are decreased in patients with melanomas as compared with those with benign nevi. We wondered why reduced autophagy should facilitate early tumor development. Using an in vitro model of melanoma tumorigenesis, in which a mutated oncogene, BRAF (v-raf murine sarcoma viral oncogene homolog B), had been introduced into normal human melanocytes, we were able to show that downregulation of ATG5 promoted the proliferation of melanocytes because it facilitated bypassing oncogene-induced senescence (OIS). Our work supports previous reports that had argued that autophagy actually suppresses tumorigenesis and explains the possible mechanism. Furthermore, our findings suggest that the status of ATG5 and autophagy could serve as a diagnostic marker for distinguishing benign from malignant tumors of melanocytes.
authors.affiliation: Institute of Pharmacology; University of Bern; Bern, Switzerland.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Pharmacology; University of Bern; Bern, Switzerland.
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: He
authors.affiliation: Institute of Pharmacology; University of Bern; Bern, Switzerland.
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
mesh_terms: D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D063646:Carcinogenesis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D016922:Cellular Senescence; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; C502071:MAP1LC3C protein, human; D008869:Microtubule-Associated Proteins
keywords: ATG5; autophagy; epigenetics; melanoma; promoter methylation; senescence