Asparagine-linked glycosylation protein 1 (ALG1) promotes aggressive phenotypes of lung adenocarcinoma cells, A549, via modulating N-linked glycosylation and ER-Stress.

Abstract

Glycosylation plays a critical role in various biological processes and is essential for cell survival. Aberrant glycosylation has been implicated in numerous diseases, including cancer. Lung cancer remains the leading cause of cancer-related mortality worldwide. The correlation between lung cancer progression and abnormal glycosylation has been demonstrated previously. Asparagine-linked glycosylation protein 1 (ALG1) is a key enzyme involved in the N-linked glycosylation process; however, its role in cancer progression remains unclear. In this study, we investigated the function of ALG1 in lung cancer progression. Analysis of the Cancer Genome Atlas (TCGA) dataset revealed that ALG1 expression was significantly upregulated in lung tumor tissues and was associated with poor patient prognosis. To explore its functional relevance, ALG1 expression was depleted in A549 lung adenocarcinoma cells using CRISPR-Cas9-mediated knockout. Loss of ALG1 led to reduced levels of protein N-linked glycosylation and induced an endoplasmic reticulum (ER)-stress response. Functionally, ALG1 knockout significantly impaired A549 cell proliferation, migration, and invasion, as evidenced by phenotypic assays and molecular markers. Moreover, the extent of glycosylation deficiency was positively correlated with ER-stress activation and inversely associated with cancer cell aggressiveness. These findings suggest that ALG1 promotes lung cancer aggressiveness through the regulation of protein glycosylation and modulation of ER-stress pathways. Overall, this study highlights the potential of ALG1 as a therapeutic target and a prognostic biomarker for lung adenocarcinoma patients.