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Objective: Desmosomes are intercellular junctions that facilitate strong cell-cell adhesion, thus providing resistance against mechanical stress for epithelial tissues.A body of evidence indicates that reduced expression of desmosomal proteins is associated with poor prognosis in various cancers.As a key component of desmosomal plaque proteins, the functional role of desmoplakin (DSP) in cancer has not yet been elucidated.The aims of this study were: (1) to analyze DSP expression in lung cancer; (2) to explore the mechanism for DSP downregulation;(3) to assess the functional role of DSP in lung cancer cells;and (4) to investigate the mechanisms by which DSP exerts its biological function.