DNAJB6 Promotes Ferroptosis in Esophageal Squamous Cell Carcinoma

Jiang, Bin; Zhao, Yongqiang; Shi, Mo; Song, Lingyun; Wang, Qiang; Qin, QiMing; Song, Xuemin; Wu, Shengyuan; Fang, Zhen; Liu, XiangYan

doi:10.1007/s10620-019-05929-4

Cited by 39 publications

(33 citation statements)

References 24 publications

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“…DNAJB6 is an HSP40 family protein that has significant influence on the inhibition of tumour growth and metastasis. Jiang et al found that DNAJB6 plays an important role in ferroptosis, and its expression is down‐regulated in the oesophageal carcinoma tissues 27 . In addition, the overexpression of DNAJB6 leads to radiosensitization of glioblastoma cells 28 .…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Zheng

Xie

et al. 2021

J Cellular Molecular Medi

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Ferroptosis is a newly discovered form of programmed cell death, which has unique biological effects on metabolism and redox biology. In this study, the prognostic value of ferroptosis‐related genes was investigated in lower‐grade gliomas (LGG). We downloaded the ferroptosis‐related genes from the FerrDb dataset. Univariate Cox and LASSO regression analyses were applied to identify genes correlated with overall survival (OS). Subsequently, 12 ferroptosis‐related genes were screened to establish the prognostic signature using stepwise multivariate Cox regression. According to the median value of risk scores, patients were divided into low‐ and high‐risk subgroups. The Kaplan‐Meier curves showed the high‐risk group had a lower OS. The predictive power of the risk model was validated using the CGGA. Functional analysis revealed that the terms associated with plasma membrane receptor complex, immune response and glutamate metabolic process were primarily related to the risk model. Moreover, we established a nomogram that had a strong forecasting ability for the 1‐, 3‐ and 5‐year OS. In addition, we compared the risk scores between different clinical features. We also detected infiltration of macrophages and monocytes in different subgroups. Overall, our study identified the prognostic signature of 12 ferroptosis‐related genes, which has the potential to predict the prognosis of LGG.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Zheng

Xie

et al. 2021

J Cellular Molecular Medi

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“…Overexpression of some genes and proteins can promote ferroptosis in cancer cells. The level of DNAJ/Hsp40 homolog subfamily B member 6 (DNAJB6) is negatively correlated with lymph node metastasis in esophageal squamous cell carcinoma (ESCC) patients, and the overexpression of its isoform DNAJB6a is accompanied by remarkable reduction in the protein levels of GPX4 and phospho-AKT (p-AKT), thus DNAJB6a plays an anti-oncogenic role in ESCC progression via ferroptosis ( 212 ). Signal transducer and activator of transcription-3 (STAT3) can promote ferroptosis through activation of cathepsin B-mediated lysosomal cell death in PANC-1 and CFPAC-1 cells ( 170 ).…”

Section: Ferroptosis and Cancermentioning

confidence: 99%

Ferroptosis: Biochemistry and Biology in Cancers

et al. 2021

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The challenge of eradicating cancer is that cancer cells possess diverse mechanisms to protect themselves from clinical strategies. Recently, ferroptosis has been shown to exhibit appreciable anti-tumor activity that could be harnessed for cancer therapy in the future. Ferroptosis is an iron-dependent form of regulated cell death that is characterized by the oxidization of polyunsaturated fatty acids (PUFAs) and accumulation of lipid peroxides. Ferroptosis has been closely correlated with numerous biological processes, such as amino acid metabolism, glutathione metabolism, iron metabolism, and lipid metabolism, as well as key regulators including GPX4, FSP1, NRF2, and p53. Although ferroptosis could be involved in killing various cancer cells, multiple aspects of this phenomenon remain unresolved. In this review, we summarize the biochemistry and biology of ferroptosis in diverse cancers and discuss the potential mechanisms of ferroptosis, which might pave the way for guiding cancer therapeutics.

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“…Nrf2 is a core transcription factor that regulates cell oxidative stress, and it exerts an antioxidant/antiapoptotic effect. Multiple studies have shown that AKT and Nrf2 / HO‐1 signaling pathways participate in the regulation of ferroptosis [ 11 , 12 ]. At the same time, the activated AKT and Nrf2 signaling pathways attenuate Erastin‐induced ferroptosis [ 13 , 14 ].…”

mentioning

confidence: 99%

Lipoxin A4 protects primary spinal cord neurons from Erastin‐induced ferroptosis by activating the Akt/Nrf2/HO‐1 signaling pathway

Wei

Liu

et al. 2021

FEBS Open Bio

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Ferroptosis is an iron‐dependent programmed cell death, which participates in the pathogenesis of spinal cord injury (SCI). Our previous study has revealed that Lipoxin A4 (LXA4) exerts a protective role in SCI. Here, we investigated whether LXA4 can protect SCI through inhibiting neuronal ferroptosis. We treated primary spinal cord neurons with Erastin (ferroptosis activator) to induce ferroptosis. Erastin treatment reduced cell viability and enhanced cell death of primary spinal cord neurons, which was rescued by ferrostatin‐1 (ferroptosis inhibitor). Moreover, Erastin repressed glutathione peroxidase 4 (GPX4) expression and the levels of glutathione and cysteine in primary spinal cord neurons. Erastin also enhanced the expression of ferroptosis biomarkers (PTGS2 and ACSL4) and the levels of reactive oxygen species (ROS) in primary spinal cord neurons. The influence conferred by Erastin was effectively abolished by LXA4 treatment. Furthermore, LXA4 enhanced the protein expression of p‐AKT, nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and haem‐oxygenase‐1 (HO‐1) in primary spinal cord neurons. LXA4‐mediated inhibition of ferroptosis of primary spinal cord neurons was prohibited by LY294002 (AKT inhibitor), brusatol (Nrf2 inhibitor) or zinc protoporphyrin (HO‐1 inhibitor). In conclusion, this work demonstrated that LXA4 exerted a neuroprotective effect in Erastin‐induced ferroptosis of primary spinal cord neurons by activating the Akt/Nrf2/HO‐1 signaling pathway. Thus, this work provides novel insights into the mechanisms of action of LXA4 in ferroptosis of primary spinal cord neurons and indicates that LXA4 may be a potential therapeutic agent for SCI.

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DNAJB6 Promotes Ferroptosis in Esophageal Squamous Cell Carcinoma

Cited by 39 publications

References 24 publications

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Ferroptosis‐related gene signature as a prognostic marker for lower‐grade gliomas

Ferroptosis: Biochemistry and Biology in Cancers

Lipoxin A4 protects primary spinal cord neurons from Erastin‐induced ferroptosis by activating the Akt/Nrf2/HO‐1 signaling pathway

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