FOXO1-mediated argininosuccinate lyase transcription inhibits ammonia metabolism and breast cancer cell metastasis.

ABSTRACT: Cancer cells exhibit altered and elevated metabolic processes to meet their increased bioenergetic and biosynthetic demands, leading to the production of ammonia as a byproduct. However, the mechanisms by which tumor cells manage excess ammonia remain poorly understood, despite its critical role in nitrogen metabolism. The urea cycle (UC), a central pathway for ammonia detoxification, has been insufficiently explored in the context of cancer metabolism. In this study, we identify Forkhead box O1 (FOXO1), a transcription factor essential for tumorigenesis and progression, as a key regulator of the UC in breast cancer cells. Specifically, FOXO1 inhibits argininosuccinate lyase (ASL) expression, a crucial enzyme in the UC, leading to reduced ammonia detoxification. Mechanistic analyses reveal

SUBMITTER: Zhao M 

PROVIDER: S-EPMC12509978 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature