title: Chronic mTOR activation promotes cell survival in Merkel cell carcinoma.
abstract: Merkel cell carcinoma (MCC) is an aggressive skin cancer with rising incidence. In this study, we demonstrate that mTOR activation and suppressed autophagy is common in MCCs. mTOR inhibition in two primary human MCC cell lines induces autophagy and cell death that is independent of caspase activation but can be attenuated by autophagy inhibition. This is the first study to evaluate mTOR and autophagy in MCC. Our data suggests a potential role of autophagic cell death upon mTOR inhibition and thus uncovers a previously underappreciated role of mTOR signaling and cell survival, and merits further studies for potential therapeutic targets.
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.|Cancer Center Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430000.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
authors.forename: Amelia
authors.initials: A
authors.lastname: McDermott
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
authors.forename: Lijian
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Kannan
authors.affiliation: University of South Florida, College of Medicine, Tampa, FL.
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Stack
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Davis
authors.affiliation: Department of Internal Medicine, Division of Dermatology, Washington University School of Medicine in St. Louis, 63110.
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Cornelius
authors.affiliation: Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D015266:Carcinoma, Merkel Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation; D005557:Formaldehyde; D006801:Humans; D016612:Paraffin Embedding; D010588:Phagosomes / Q000201:enzymology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016707:Tissue Fixation; D015854:Up-Regulation
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D047428:Protein Kinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D005557:Formaldehyde; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020169:Caspases
keywords: Autophagy; Cell death; Merkel cell carcinoma; mTOR inhibitor; mTOR pathway