Association of deubiquitin ligase and cell surface molecules regulates the pathophysiology of malignant pleural mesothelioma

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Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial lining of pleura. It is generally associated with a history of asbestos exposure and has a very poor prognosis. We found that expression of CD26 upregulates periostin secretion by MPM cells, leading to enhanced MPM cell migratory and invasive activity. CD26 potentiates tumor cell invasion through its interaction with alpha5 beta1 integrin, and CD9 negatively regulates tumor cell invasion by reducing the level of CD26-alpha5 beta1 integrin complex through an inverse correlation between CD9 and CD26 expression. We also showed CD26 associated with somatostatin (SST) receptor 4 and this interaction regulates the growth of MPM cells. Moreover, CD26 is also associated with deubiquitin ligase22 (USP22) which regulated the invasion and metastasis of CD26 positive mesothelioma cells and actually these molecules colocalized in the tissue samples of malignant mesothelioma.