SUMO-activating enzyme subunit 1 (SAE1) promotes non-small cell lung cancer metastasis by promoting the epithelial-mesenchymal transition through the SUMOylation of N-cadherin.

Abstract

Protein SUMOylation is a newly discovered process similar to protein ubiquitination and is crucial for protein stability and protein localization. SAE1 is an important enzyme that initiates protein SUMOylation, but its role in the progression of non-small cell lung cancer remains unknown. We analyzed the protein expression profiles of non-small cell lung cancer tissues and single-cell sequencing data and confirmed that SAE1 is highly expressed in non-small cell lung cancer cells and is associated with a malignant phenotype. Knockdown of SAE1 decreased the growth, cell cycle progression, and metastasis of non-small cell lung cancer cells both in vitro and in vivo. Mechanistically, using the protein expression profile of non-small cell lung cancer cell lines with altered SAE1 expression, we showed that SAE1, a key molecule mediating protein SUMOylation, can SUMOylate the epithelial-mesenchymal transition-related protein N-cadherin, stabilize N-cadherin and promote the occurrence of the EMT in non-small cell lung cancer cells, leading to lung cancer invasion and metastasis. In clinical application, we used sputum samples from patients with lung cancer or chronic pulmonary obstructive pulmonary disease for protein profiling and further used sputum-based thin-slice technology for experimental verification, which confirmed the application potential of SAE1 in the diagnosis of lung cancer patients. In summary, our findings reveal a critical role for SAE1 as an oncogene in lung cancer cells and suggest that SAE1 may be used for the diagnosis of lung cancer patients.