benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and Carcinoma--Merkel-Cell

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.

Topics: Amino Acid Chloromethyl Ketones; Carcinoma, Merkel Cell; Caspases; Cell Line, Tumor; Cell Survival; Enzyme Activation; Formaldehyde; Humans; Paraffin Embedding; Phagosomes; Protein Kinase Inhibitors; Skin Neoplasms; Tissue Fixation; TOR Serine-Threonine Kinases; Up-Regulation