Increased ATF2 expression predicts poor prognosis and inhibits sorafenib-induced ferroptosis in gastric cancer

Xu, Xin; Li, Yaxian; Wu, Youliang; Wang, Mingliang; Lu, Yida; Fang, Zi-Qing; Wang, Huizhen; Li, Yongxiang

doi:10.1016/j.redox.2022.102564

Cited by 40 publications

(25 citation statements)

References 53 publications

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“…ATF2 belongs to the activating protein‐1 (AP1) transcription factor family, which mediates cellular responses to stimuli and the tumorigenesis and progression of many cancers (Inoue et al, 2018). In GC, high expression of ATF2 was associated with poor outcome and attenuated sorafenib‐evoked ferroptosis in GC (Xu et al, 2022). In the current work, an increased ATF2 was shown in GC tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

Amentoflavone attenuates cell proliferation and induces ferroptosis in human gastric cancer by miR‐496/ATF2 axis

Tang

Gao

et al. 2023

Chem Biol Drug Des

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Amentoflavone (AF) is a natural multifunctional biflavonoid that has been revealed to possess multiple biological activities, including anticancer activity. Here, this work focused on exploring the functions and mechanism of AF in gastric cancer (GC). Levels of genes and proteins were examined by quantitative real‐time PCR and western blotting. Cell proliferation and cell death were analyzed using cell counting kit‐8, colony formation, and lactate dehydrogenase (LDH) release assay, respectively. Cell ferroptosis was evaluated by detecting the levels of malondialdehyde (MDA), reduced glutathione (GSH), Fe2+, and intracellular reactive oxygen species (ROS). The binding between miR‐496 and activating transcription factor 2 (ATF2) was confirmed by using dual‐luciferase reporter assay. Murine xenograft assay was conducted for in vivo experiments. The results showed that AF suppressed the proliferation and induced ferroptotic cell death in GC cells. MiR‐496 expression was decreased in GC tissues and cells, and AF treatment increased miR‐496 expression level in GC cells. Functionally, miR‐496 inhibition reversed the inhibitory effects of AF on GC cell proliferation and promoting effects on ferroptotic cell death. Mechanistically, ATF2 was targeted by miR‐496. ATF2 expression was increased in GC tissues and cells, which was decreased by AF treatment and subsequently rescued by miR‐496 downregulation in GC cells. Moreover, miR‐496 overexpression suppressed the proliferation and induced ferroptotic cell death in GC cells via targeting ATF2. In all, AF suppressed the proliferation and induced ferroptotic cell death in GC cells via miR‐496/ATF2 axis, indicating a novel therapeutic approach for GC patients.

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Section: Discussionmentioning

confidence: 99%

Amentoflavone attenuates cell proliferation and induces ferroptosis in human gastric cancer by miR‐496/ATF2 axis

Tang

Gao

et al. 2023

Chem Biol Drug Des

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“…Moreover, the elevated expression of transcription factor ATF2, has been observed in GC tissue, indicating a poor prognosis. In contrast, inhibiting ATF2 significantly suppressed the malignant phenotype of GC cells 124 . In contrast to ATF2, another member of the activated transcription factor family, ATF3, exhibited low expression in GC tissues and cells and was positively correlated with patient survival 125 .…”

Section: Ferroptosis In Gcmentioning

confidence: 97%

“…160 Similarly, activation of ATF2 during sorafenib-induced ferroptosis has been observed, and knockdown of ATF2 was found to promote sorafenib-induced ferroptosis achieved through the inhibition of SLC7A11 expression mediated by HSPH1, a downstream target of ATF2. 124 Baicalin, a flavonoid derived from Scutellaria baicalensis Georgi, has been demonstrated to enhance the effectiveness of 5-fluorouracil in GC by promoting ROS-mediated ferroptosis. 161 Furthermore, STAT3 has been recognized as a modulator of crucial ferroptosis-related genes, including GPX4, SLC7A11, and FTH1.…”

Section: Ferroptosis Improves Drug Resistance In Gcmentioning

confidence: 99%

Targeting ferroptosis in gastric cancer: Strategies and opportunities

Le,

Pan,

Zhang

et al. 2023

Immunological Reviews

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SummaryFerroptosis is a novel form of programmed cell death morphologically, genetically, and biochemically distinct from other cell death pathways and characterized by the accumulation of iron‐dependent lipid peroxides and oxidative damage. It is now understood that ferroptosis plays an essential role in various biological processes, especially in the metabolism of iron, lipids, and amino acids. Gastric cancer (GC) is a prevalent malignant tumor worldwide with low early diagnosis rates and high metastasis rates, accounting for its relatively poor prognosis. Although chemotherapy is commonly used to treat GC, drug resistance often leads to poor therapeutic outcomes. In the last several years, extensive research on ferroptosis has highlighted its significant potential in GC therapy, providing a promising strategy to address drug resistance associated with standard cancer therapies. In this review, we offer an extensive summary of the key regulatory factors related to the mechanisms underlying ferroptosis. Various inducers and inhibitors specifically targeting ferroptosis are uncovered. Additionally, we explore the prospective applications and outcomes of these agents in the field of GC therapy, emphasizing their capacity to improve the outcomes of this patient population.

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“…12 It has been established that ferroptosis is involved in the initiation and progression of many diseases. These diseases (Figure 2) included stroke, 13 colorectal cancer, 14 hepatocellular carcinoma, 15 glaucoma, 16 oral squamous cell carcinoma, 17 traumatic brain injury, 18 acute and chronic kidney diseases, 19 cerebral ischemia-reperfusion injury, 20 spinal cord injury, 18 lung cancer, 21 gastric cancer, 22 gallbladder carcinoma, 23 cardiovascular disease, 24 thyroid cancer, 25 chronic obstructive pulmonary disease, 26 ovarian cancer, 27 cervical cancer, 28 diabetes 29,30 and nonalcoholic fatty liver disease. 31 Furthermore, ferroptosis is closely related to many disease processes, such as oxidative stress, 32 inflammatory response 33 and autophagy.…”

Section: Introductionmentioning

confidence: 99%

Narrative review of ferroptosis in obesity

Zhou

2023

J Cellular Molecular Medi

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Obesity is widely recognized as a major global health problem caused by a chronic energy imbalance resulting from a combination of excess caloric intake and insufficient energy expenditure. Excessive energy intake and physical inactivity are traditional risk factors for obesity. Obesity is a risk factor for many diseases, including hypertension, diabetes and tumours. Recent studies have found a strong link between ferroptosis and obesity. Ferroptosis is an iron‐dependent regulated cell death caused by iron overload and reactive oxygen species‐dependent excessive accumulation of lipid peroxidation. Ferroptosis is involved in many biological processes, such as amino acid metabolism, iron metabolism and lipid metabolism. Some potential strategies to reduce the adverse effects of ferroptosis on obesity are suggested and future research priorities are highlighted.

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Increased ATF2 expression predicts poor prognosis and inhibits sorafenib-induced ferroptosis in gastric cancer

Cited by 40 publications

References 53 publications

Amentoflavone attenuates cell proliferation and induces ferroptosis in human gastric cancer by miR‐496/ATF2 axis

Amentoflavone attenuates cell proliferation and induces ferroptosis in human gastric cancer by miR‐496/ATF2 axis

Targeting ferroptosis in gastric cancer: Strategies and opportunities

Narrative review of ferroptosis in obesity

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