UBE2L3 promotes lung adenocarcinoma invasion and metastasis through the GSK-3 beta/Snail signaling pathway

Lung cancer is the leading cause of cancer-related mortality, and the deaths are mostly attributed to distant metastasis. Previous studies have demonstrated that ubiquitin-conjugating enzyme E2 L3 (UBE2L3) mediates the progression of many human cancers. However, the roles and molecular mechanisms of UBE2L3 in invasion and metastasis of lung adenocarcinoma (LUAD) are yet to be fully understood. Here, we studied the expression pattern of UBE2L3 and demonstrated that it is dramatically up-regulated in LUAD tissues compared with the normal tissues, and its overexpression is positively correlated with lymph node metastasis. Moreover, the upregulation of UBEE2L3 in LUAD tissues is associated with shorter overall survival (OS). UBE2L3 silencing impairs the metastatic capacity of LUAD cells in vitro and in vivo, while its overexpression confers an opposite effect. In addition, our data showed that UBE2L3 promotes cancer cells epithelial-mesenchymal transition (EMT) and metastasis via the glycogen synthase kinase 3 beta(GSK-3 beta)/Snail axis. Besides, UBE2L3 was shown to promote ubiquitination and degradation of the GSK-3 beta. Immunohistochemical analysis demonstrated that UBE2L3 expression is positively correlated with Snail, but negatively correlated with GSK-3 beta and E-cadherin in LUAD tissues. Taken together, our findings demonstrated that UBE2L3 modulates metastasis of LUAD cells.

Automated summary

The expression of ubiquitin-conjugating enzyme E2 L3 (UBE2L3) is dramatically up-regulated in lung adenocarcinoma (LUAD). UBE2L3 overexpression is correlated with lymph node metastasis and shorter overall survival. It promotes cancer cell epithelial-mesenchymal transition and metastasis via the GSK-3β/Snail axis.