ACAT1 Induces the Differentiation of Glioblastoma Cells by Rewiring Choline Metabolism

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2024 Nov 4

PMID 39494339

Authors

Shen You

Ming-Jin Wang

Zhen-Yan Hou

Wei-Da Wang

Zhi-Hui Zhang

Ting-Ting Du

Shu-Ying Li

Yi-Chen Liu

Ni-Na Xue

Xiao-Min Hu

Xiao-Guang Chen

Ming Ji

Affiliations

Soon will be listed here.

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, which is crucial for the differentiation of GBM cells. Finally, we demonstrated that a naturally available substance, chlorogenic acid (CHA), could inhibit phosphorylation of ACAT1 and so delay GBM progression, CHA is a promising candidate to treat GBM because it could induce the differentiation of cancer cells.

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