Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells

Sun, Yan; Berleth, Niklas; Wu, Wenxian; Schlütermann, David; Deitersen, Jana; Stuhldreier, Fabian; Berning, Lena; Friedrich, Anja; Akgün, Seda; Mendiburo, María José; Wesselborg, Sebastian; Conrad, Marcus; Berndt, Carsten; Stork, Björn

doi:10.1038/s41419-021-04306-2

Cited by 126 publications

(68 citation statements)

References 61 publications

(74 reference statements)

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“…Pretreatment with FG-4592, an inhibitor of prolyl hydroxylase of HIF, reduces renal injury via AKT/GSK-3β-mediated activation of Nrf2 in advanced stages of ferroptosis [ 32 ]. In addition, Yadong Sun et al reported that cancer spheroids proliferate using mammalian targets of rapamycin (mTOR) and utilize the lipid peroxidase GPX4 against ferroptosis [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-related long non-coding RNA signature predicts the prognosis of bladder cancer

Hou

Cheng

et al. 2022

BMC Cancer

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Background Ferroptosis is an iron-dependent programmed cell death modality that may have a tumor-suppressive function. Therefore, regulating ferroptosis in tumor cells could serve as a novel therapeutic approach. This article focuses on ferroptosis-associated long non-coding RNAs (lncRNAs) and their potential application as a prognostic predictor for bladder cancer (BCa). Methods We retrieved BCa-related transcriptome information and clinical information from the TCGA database and ferroptosis-related gene sets from the FerrDb database. Least absolute shrinkage and selection operator regression (LASSO) and Cox regression models were used to identify and develop predictive models and validate the model accuracy. Finally, we explored the inter-regulatory relationships between ferroptosis-related genes and immune cell infiltration, immune checkpoints, and m6A methylation genes. Results Kaplan–Meier analyses screened 11 differentially expressed lncRNAs associated with poor BCa prognosis. The signature (AUC = 0.720) could be utilized to predict BCa prognosis. Additionally, GSEA revealed immune and tumor-related pathways in the low-risk group. TCGA showed that the p53 signaling pathway, ferroptosis, Kaposi sarcoma − associated herpesvirus infection, IL − 17 signaling pathway, MicroRNAs in cancer, TNF signaling pathway, PI3K − Akt signaling pathway and HIF − 1 signaling pathway were significantly different from those in the high-risk group. Immune checkpoints, such as PDCD-1 (PD-1), CTLA4, and LAG3, were differentially expressed between the two risk groups. m6A methylation-related genes were significantly differentially expressed between the two risk groups. Conclusion A new ferroptosis-associated lncRNAs signature developed for predicting the prognosis of BCa patients will improve the treatment and management of BCa patients.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis-related long non-coding RNA signature predicts the prognosis of bladder cancer

Hou

Cheng

et al. 2022

BMC Cancer

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“…It has been reported that FRGs are involved in the regulation of drug-induced ferroptosis in BLCA ( 11 ). Additionally, FRG-related inducers have been found to suppress BC with the help of mTOR inhibitors ( 19 ). Recently, ferroptosis participates in the inhibition of cell cycle in BC by obstructing the G0/G1 phase ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Signature Based on Ferroptosis-Related Genes Predicts the Prognosis of Patients With Advanced Bladder Urothelial Carcinoma

Huang

Chen

et al. 2021

Front. Oncol.

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Bladder Urothelial Carcinoma (BLCA) is the major subtype of bladder cancer, and the prognosis prediction of BLCA is difficult. Ferroptosis is a newly discovered iron-dependent cell death pathway. However, the clinical value of ferroptosis-related genes (FRGs) on the prediction of BLCA prognosis is still uncertain. In this study, we aimed to construct a novel prognostic signature to improve the prognosis prediction of advanced BLCA based on FRGs. In the TCGA cohort, we identified 23 differentially expressed genes (DEGs) associated with overall survival (OS) via univariate Cox analysis (all P < 0.05). 8 optimal DEGs were finally screened to generate the prognostic risk signature through LASSO regression analysis. Patients were divided into two risk groups based on the median risk score. Survival analyses revealed that the OS rate in the high-risk group was significantly lower than that in the low-risk group. Moreover, the risk score was determined as an independent predictor of OS by the multivariate Cox regression analysis (Hazard ratio > 1, 95% CI = 1.724-2.943, P < 0.05). Many potential ferroptosis-related pathways were identified in the enrichment analysis in BLCA. With the aid of an external FAHWMU cohort (n = 180), the clinical predication value of the signature was further verified. In conclusion, the prognosis of advanced BLCA could be accurately predicted by this novel FRG-signature.

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“…Sun et al. showed that FIN56 can induce ferroptosis in bladder cancer cells and can be enhanced by combination with the mTOR inhibitor, Torin 2 ( 143 ). Zhang et al.…”

Section: Caspase-independent Rcd In Targeted Therapymentioning

confidence: 99%

Application of Regulatory Cell Death in Cancer: Based on Targeted Therapy and Immunotherapy

Che

et al. 2022

Front. Immunol.

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The development of cancer treatment methods is constantly changing. For common cancers, our treatment methods are still based on conventional treatment methods, such as chemotherapy, radiotherapy, and targeted drug therapy. Nevertheless, the emergence of tumor resistance has a negative impact on treatment. Regulated cell death is a gene-regulated mode of programmed cell death. After receiving specific signal transduction, cells change their physical and chemical properties and the extracellular microenvironment, resulting in structural destruction and decomposition. As research accumulates, we now know that by precisely inducing specific cell death patterns, we can treat cancer with less collateral damage than other treatments. Many newly discovered types of RCD are thought to be useful for cancer treatment. However, some experimental results suggest that some RCDs are not sensitive to cancer cell death, and some may even promote cancer progression. This review summarizes the discovered types of RCDs, reviews their clinical efficacy in cancer treatment, explores their anticancer mechanisms, and discusses the feasibility of some newly discovered RCDs for cancer treatment in combination with the immune and tumor microenvironment.

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Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells

Cited by 126 publications

References 61 publications

Ferroptosis-related long non-coding RNA signature predicts the prognosis of bladder cancer

Ferroptosis-related long non-coding RNA signature predicts the prognosis of bladder cancer

A Novel Prognostic Signature Based on Ferroptosis-Related Genes Predicts the Prognosis of Patients With Advanced Bladder Urothelial Carcinoma

Application of Regulatory Cell Death in Cancer: Based on Targeted Therapy and Immunotherapy

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