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

恶性胸膜间皮瘤（MPM）是一种起源于胸膜间皮层的侵袭性恶性肿瘤。它通常与石棉接触史有关，预后很差。我们发现CD26的表达上调MPM细胞的骨膜蛋白分泌，导致MPM细胞迁移和侵袭活性增强。CD26通过与alpha5 beta1整合素的相互作用增强肿瘤细胞的侵袭，CD9通过CD9与CD26表达呈负相关关系，降低CD26-alpha5 beta1整合素复合物的水平，负向调节肿瘤细胞的侵袭。我们还发现CD26与生长抑素（SST）受体4相关，这种相互作用调节MPM细胞的生长。此外，CD26还与调节CD26阳性间皮瘤细胞侵袭和转移的去泛素连接酶22 （deubiquitin ligase22, USP22）相关，实际上这些分子在恶性间皮瘤组织样本中存在共定位。

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.