Overexpression of alcohol dehydrogenase 1 A inhibits the progress of triple negative breast cancer via Wnt/β-catenin signaling.

The identification of novel therapeutic targets in triple negative breast cancer (TNBC) continues to be of paramount importance. In this context, ADH1A (Alcohol Dehydrogenase 1 A), a protein involved in tyrosine metabolism, was comprehensively examined to assess its expression and functional roles in TNBC. A combination of bioinformatics approaches and local tissue analyses was utilized to determine the expression levels of ADH1A in TNBC samples. Genetic manipulation techniques were employed to alter ADH1A expression, and the subsequent effects on TNBC cell behavior were systematically analyzed. This study is the first to report on the alterations of 14 genes related to tyrosine metabolism within the TCGA-TNBC cohorts. Notably, reduced expression of these enzymes is associated with poorer survival outcomes in patients with TNBC. An analysis of the TCGA database revealed reduced levels of ADH1A in human TNBC tissues. Furthermore, ADH1A protein expression was diminished in TNBC tissues of patients who received local treatment, in contrast to the elevated expression observed in adjacent normal tissues. In the MDA-MB-231 and SUM159PT cell lines, ADH1A knockdown significantly promoted cell proliferation, migration, and invasion. On the contrary, ADH1A overexpression inhibited cell proliferation, migration, and invasion, while inducing cell apoptosis. Mechanistically, the overexpression of ADH1A may attenuate the malignant characteristics of TNBC cells by inhibiting the Wnt/β-catenin signaling pathway. In conclusion, ADH1A may be a useful biomarker for TNBC prognosis. This study is the first to reveal that ADH1A inhibits the malignant progression of TNBC via the Wnt/β-catenin signaling pathway.