ACAT1 Induces the Differentiation of Glioblastoma Cells by Rewiring Choline Metabolism.

ABSTRACT: Abnormal differentiation of cells is a hallmark of malignancy. Induction of cancer-cell differentiation is emerging as a novel therapeutic strategy with low toxicity in hematological malignances, but whether such treatment can be used in solid tumors is not known. Here, we uncovered a novel function of acetyl coenzyme A acetyltransferase (ACAT1) in regulating the differentiation of glioblastoma (GBM) cells. Inhibition of ACAT1 promoted the differentiation of GBM cells into astrocytes but also delayed tumor growth. Mechanistically, suppression of ACAT1 restored mitochondrial function and led to metabolic "reprogramming" in GBM cells: reduction of fatty-acid oxidation and acetyl-CoA, but an increase in free fatty acids. Importantly, ACAT1 negatively regulated the choline metabolic pathway, w

SUBMITTER: You S 

PROVIDER: S-EPMC11528465 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature