Lung adenocarcinoma (LUAD) is a lethal malignancy with metastasis, a major tumor feature that predominantly correlated with progression, but the molecules that mediated tumor metastasis remain elusive. To declare the critical regulatory genes, RNA sequencing data in LUAD patients was acquired from The Cancer Genome Atlas (TCGA) and found that ALDH3A1 was distinctly highly expressed in LUAD patients with metastasis (M1) compared with those without metastasis (M0), linked to the property of cancer stem cell and epithelial-mesenchymal transition (EMT). Besides, high ALDH3A1 expression predicted a poor prognosis. Knockdown of ALDH3A1 showed decreased proliferation, migration, and invasion in A549 cell line. Furthermore, BAG1 was regulated by ALDH3A1 through p53, enhanced cell proliferation, and predicted clinical prognosis. Our findings collectively uncovered a novel mechanism that orchestrates tumor cells' metastasis, and decreasing ALDH3A1 represented a potential therapeutic target for reprogramming metastasis.

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