The function and mechanism of ferroptosis in cancer

Wang, Ying; Wei, Zihao; Pan, Keran; Li, Jing; Chen, Qianming

doi:10.1007/s10495-020-01638-w

Cited by 144 publications

(105 citation statements)

References 109 publications

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“…Stromal components of the TME had lots of crosstalks with tumor cells. Such crosstalks could shape the TME into a tumor-promoting one through multiple ways, including Epithelial-mesenchymal transition (EMT), inhibition of ferroptosis and autophagy ( 11 ), influencing energy metabolism ( 12 ) and tumor infiltrated immune cells (TIICs) ( 13 ). EMT presented as an essential mechanism of tumor invasion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

Miao

Jiang

et al. 2021

Front. Oncol.

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The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients’ responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine.

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Section: Introductionmentioning

confidence: 99%

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

Miao

Jiang

et al. 2021

Front. Oncol.

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“…Iron is one of the most abundant trace elements in cells, and its overload is thought to be one of biomarkers of ferroptosis which has been recently defined to be an iron-dependent form of programmed cell death. 49,50 Cancer cells usually contain high concentration of glutathione (GSH) which scavenges reactive oxygen species (ROS), inhibiting ferroptosis and lead to resistant to cisplatin. 51 Therefore, Erastin and GPX4 inhibitors were applied to induce ferroptosis of cisplatin-resistant cancer cells.…”

Section: Resultsmentioning

confidence: 99%

The Disturbance of Anticancer Drug Cisplatin to Cellular Homeostasis of Trace Elements Revealed by ICP-MS and ToF-SIMS

Jia¹,

Li²,

Zhang³

et al. 2021

At.Spectrosc.

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Trace elements play important roles in many physiological processes. The disorder in the metabolism and/or homeostasis of the trace elements will cause pathogenic changes, and finally lead to the development of diseases. This present work aimed to investigate the effect of anticancer metallodrug cisplatin on the homeostasis of trace metal elements, iron (Fe), zinc (Zn) and copper (Cu), in both human HEK293 normal cells and A549 lung cancer cells by using inductively coupled plasma mass spectrometry (ICP-MS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The levels of trace metal elements in both whole cells and nuclei subjected to cisplatin treatment were measured by ICP-MS, and results showed that accompanying with the increasing concentration of cisplatin, the content of Fe inside whole cells and nuclei of both normal and cancer cells increased, implying that cisplatin may induce ferroptosis, contributing to its anticancer activity. While the level of Cu and Zn in the whole cells increased with increase in cisplatin concentration, the level of Cu and Zn, in particular the latter, in nuclei decreased with increase of cisplatin concentration. These implicate that cisplatin may compete with Zn for binding to metalloproteins in nuclei, leading to efflux of Zn from nucleus. The normalized signal intensity of Fe, Zn, and Cu in single cells detected by ToF-SIMS increased accompanying with increased cisplatin concentration, being in line with that obtained by quantitative ICP-MS on large quantity of cells. These findings provide novel insights into better understanding in the mechanism of action of cisplatin.Trace metal elements, such as iron, zinc, copper, are essential in the human body as they consist of many metalloproteins or enzymes which are involved in vital physiological regulation processes and play crucial roles in maintaining the normal function

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“…Accumulating evidence have indicated that ferroptosis played a vital role in tumor biology [15] . It has recently been shown that promotion of ferroptosis could be exploited to treat cancer, and ferroptosis inducers exhibited great potential to improve therapeutic performance [16,19] . For instance, Markowitsch et al have demonstrated that artesunate could inhibit growth of sunitinib-resistant renal cell carcinoma cells through cell cycle arrest and induction of ferroptosis [20] .…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Robust Ferroptosis-Related Prognostic Signature to Predict Overall Survival in Clear Cell Renal Cell Carcinoma

Lin¹,

Li²,

Chen³

2021

Preprint

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Background: Ferroptosis is a novel defined type of programmed cell death (PCD) with widespread functions involved in physical conditions or multiple diseases including malignancies. However, the relationship between ccRCC and ferroptosis-related regulators remains poorly known. Herein, we investigate the prognostic values and potential mechanisms of ferroptosis-related genes (FRGs) in ccRCC.Methods: Ferroptosis-related genes were obtained from FerrDb database, GeneCards database and previously published literatures. The gene expression profile of ferroptosis-related regulators and corresponding clinicopathological information were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed ferroptosis-related genes (DE-FRGs) were screened between ccRCC specimens and noncancerous specimens. Among these genes, prognostic DE-FRGs were identified using univariate COX analysis and LASSO regression analysis. Further multivariate COX regression was employed to identify prognosis-related hub DE-FRGs and establish a prognostic model. Results: We identified seven hub genes (HMGCR, MT1G, BID, EIF4A1, FOXM1, TFAP2C and CHAC1) from the DE-FRGs using univariate Cox regression analysis, LASSO and multivariate Cox regression analysis, and used them to establish a novel clinical predictive model in the TCGA train cohort (n = 374). Subsequently, we assessed the prognostic value of the model. Survival analysis showed that high-risk patients had a reduced overall survival (OS), the time-dependent receiver operating characteristic (ROC) curve analysis confirmed the signature's diagnostic performance. Additionally, multivariate Cox regression analysis suggested that the risk score was an independent prognostic factor. Additionally, we verified the prognostic performance of the risk model in the testing cohort (n=156), and the entire group (n=530) using Kaplan-Meier curve and ROC curve analyses. Functional analysis indicated that several carcinogenic pathways were enriched, and tumor-infiltrating immune cell abundances, and the expression levels of immunosuppressive molecules were different between two risk groups. Finally, external databases (ONCMINE, GEPIA, HPA, Kaplan-Meier plotter and cbioportal) were used to confirm the expression patterns, prognostic value, and genetic mutations of 7 hub FRGs in ccRCC.Conclusions: Collectively, we successfully constructed a novel ferroptosis-related risk signature that was significantly associated with the prognosis of ccRCC.

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The function and mechanism of ferroptosis in cancer

Cited by 144 publications

References 109 publications

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

The Disturbance of Anticancer Drug Cisplatin to Cellular Homeostasis of Trace Elements Revealed by ICP-MS and ToF-SIMS

Development and Validation of a Robust Ferroptosis-Related Prognostic Signature to Predict Overall Survival in Clear Cell Renal Cell Carcinoma

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