An inhibition of p62/SQSTM1 caused autophagic cell death of several human carcinoma cells.
Bottom Line: Electron microscopical analysis revealed the formation of autophagosomes with multilayer membranes caused by p62-silencing. p62 silencing-mediated reduced cell viability was restored by both genomic and pharmacological inhibition of autophagy but not that of apoptosis.These findings were also detected in several types of carcinoma cell lines including adenocarcinomas and squamous cell carcinomas.Results of our present study revealed that an inhibition of p62 resulted in the formation of mis-regulated autophagosomes with multilayer membranes and an autophagic cell death, and p62 can therefore be an attractive target for the development of anti-neoplastic agents.
Affiliation: Department of Pathology, School of Medicine, Tohoku University, Sendai, Japan.Show MeSH
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Mentions: We examined the effects of autophagic cell death on cell viability and cell death of various carcinoma cells other than lung adenocarcinoma cell lines in order to confirm whether the above were specific in lung adenocarcinoma or not. Autophagic cell death induced by p62-silencing was also detected in various carcinoma cells; PANC-1 (pancreatic adenocarcinoma), ECGI-10 (esophageal squamous cell carcinoma (SCC)), HSC-4 (oral SCC) and HSC-1 (skin SCC) (Fig.7a). Restoration of cell viability by autophagy inhibition in p62-silenced cells were also detected in all these carcinoma cell lines examined (Fig.7b).
Affiliation: Department of Pathology, School of Medicine, Tohoku University, Sendai, Japan.