Acetyl-CoA Acetyltransferase 2 Confers Radioresistance by Inhibiting Ferroptosis in Esophageal Squamous Cell Carcinoma

Heng, Jing-Hua; Li, Zhi-Mao; Liu, Luxin; Zheng, Zhen-Yuan; Zheng, Ya-Qi; Xu, Xiu‐E; Liao, Lian‐Di; Xu, Hanbing; Huang, Huaiyi; Li, En-Min; Xu, Li‐Yan

doi:10.1016/j.ijrobp.2023.05.031

Cited by 4 publications

(1 citation statement)

References 47 publications

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“…Glutathione peroxidase 4 is recognized as a negative regulator of ferroptosis, and cysteine is the rate-limiting amino acid for glutathione production. Acetyl-CoA acetyltransferase 2 (ACAT2) overexpression confers radioresistance by inhibiting ESCC ferroptosis, and after knockdown of ACAT2, cells can produce higher ROS after IR and increase radiosensitization by reducing glutathione peroxidase 4 levels [ 59 ].…”

Section: Cellular Regulation Mechanisms Of Radioresistancementioning

confidence: 99%

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

An,

Li,

Jia

2023

Mol Cancer

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Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-related mortality worldwide, with more than half of them occurred in China. Radiotherapy (RT) has been widely used for treating ESCC. However, radiation-induced DNA damage response (DDR) can promote the release of cytokines and chemokines, and triggers inflammatory reactions and changes in the tumor microenvironment (TME), thereby inhibiting the immune function and causing the invasion and metastasis of ESCC. Radioresistance is the major cause of disease progression and mortality in cancer, and it is associated with heterogeneity. Therefore, a better understanding of the radioresistance mechanisms may generate more reversal strategies to improve the cure rates and survival periods of ESCC patients. We mainly summarized the possible mechanisms of radioresistance in order to reveal new targets for ESCC therapy. Then we summarized and compared the current strategies to reverse radioresistance.

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Section: Cellular Regulation Mechanisms Of Radioresistancementioning

confidence: 99%

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

An,

Li,

Jia

2023

Mol Cancer

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Chemical probes for the identification of the molecular targets of honokiol

Vázquez-Villa,

Rueda-Zubiaurre,

Fernández

et al. 2025

European Journal of Medicinal Chemistry

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ACAT2 suppresses the ubiquitination of YAP1 to enhance the proliferation and metastasis ability of gastric cancer via the upregulation of SETD7

Zhang,

Cai,

Guo

et al. 2024

Cell Death Dis

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The contributions of aberrantly expressed metabolic enzymes to gastric cancer (GC) initiation and progression have been widely appreciated in recent years. Acetyl-CoA acetyltransferase 2 (ACAT2) is one member of the acetyl- CoA thiolase family. Previous studies demonstrated that ACAT2 either promotes or suppresses tumor progression in different conditions. However, the function and mechanisms of ACAT2 in GC remain unknown. We found that the expression of this enzyme was significantly increased in GC tissues compared with normal counterparts, which prompted us to further investigate the roles of this protein in GC biology. In vitro functional studies showed that ACAT2 knockdown markedly halted the proliferation and the motility of GC cells; these functions favoring malignant phenotypes of GC cells were further validated in animal experiments. Mechanistically, ACAT2 depletion significantly reduced the transcription of SETD7, which is a histone methyltransferase and plays critical roles in GC cells. We found that the pro-tumoral functions of ACAT2 were largely dependent on SETD7. Moreover, SETD7 decreased the ubiquitination level of Yes-associated protein 1 (YAP1), thereby protecting YAP1 from proteasome degradation. Increased YAP1 protein expression remarkably activated the YAP1/TAZ-TEAD1 signaling pathway, which further boosted the malignant phenotypes in GC cells. In conclusion, these findings highlight the pro-tumoral functions and molecular underpinnings of ACAT2 in GC cells, and suggest that ACAT2 could be a promising target in GC treatment.

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Acetyl-CoA Acetyltransferase 2 Confers Radioresistance by Inhibiting Ferroptosis in Esophageal Squamous Cell Carcinoma

Cited by 4 publications

References 47 publications

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

Chemical probes for the identification of the molecular targets of honokiol

ACAT2 suppresses the ubiquitination of YAP1 to enhance the proliferation and metastasis ability of gastric cancer via the upregulation of SETD7

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