Aldh1a1, short for aldehyde dehydrogenase 1 family member A1, is an enzyme in retinoic acid biosynthesis and redox balance [2]. It can metabolize reactive aldehydes to their corresponding carboxylic acid derivatives and plays important physiological and toxicological roles in areas like the CNS, metabolic disorders, and cancers [7]. The cytosolic Aldh1a1 can irreversibly convert retinal to retinoic acid, initiating RA signaling, which is crucial for self-renewal and epithelial-to-mesenchymal transition (EMT) [5].

In cancer research, genetic silencing of Aldh1a1 in in vitro, xenografted zebrafish and murine models has shown its significance. In breast cancer, Aldh1a1 enzymatic activity promotes breast tumor growth by decreasing intracellular pH, phosphorylating TAK1, activating NFκB signaling, and increasing GM-CSF secretion, leading to myeloid-derived suppressor cell expansion and immunosuppression. Inhibiting Aldh1a1 with disulfiram and gemcitabine cooperatively suppresses breast tumor growth [1]. In prostate cancer, Aldh1a1 positively regulates tumor cell survival in circulation, extravasation, and metastatic dissemination, and its gain in bone metastases is associated with high PLK3 expression [3]. In EGFR-mutant lung cancer, genetic repression of Aldh1a1 in cancer cells reduces brain metastasis [4]. In glioblastoma, overexpressing Aldh1a1 in U87 cells increases cell growth and invasion, and inhibiting AKT phosphorylation mitigates these effects [6].

In conclusion, Aldh1a1 is a key enzyme in retinoic acid biosynthesis and redox balance. Through gene-knockout or silencing in model organisms, its roles in cancer progression, metastasis, and immune-related processes have been revealed. Targeting Aldh1a1 shows potential as a therapeutic strategy in various cancers, highlighting its importance in understanding disease mechanisms and developing new treatments.