Peptides derived from histidine and methionine‐rich regions of copper transporter 1 exhibit anti‐angiogenic property by chelating extracellular Cu

Narayanan, Iyer Gomathy; Natarajan, Sulochana Konerirajapuram

doi:10.1111/cbdd.13145

Cited by 10 publications

(4 citation statements)

References 41 publications

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“…It can not only activate the main factors of angiogenesis by HIF-1, but also combine with angiogenin to promote angiogenesis (59). In human umbilical vein endothelial cells (HUVECs), the downregulation of CTR1 prevented copper from entering vascular endothelial cells and reduced angiogenesis (60). Another experiment is in line with the above conclusion.…”

Section: Ctr1supporting

confidence: 59%

The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression

Zhao

2023

Front. Oncol.

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Currently, cancer has become one of the major public health problems worldwide. Apoptosis is an important anti-cancer defense mechanism, which is used in the development of targeted drugs. Because cancer cells have endogenous resistance to apoptosis,the clinical efficacy of related drugs is not ideal. Therefore, non-apoptotic regulatory cell death may bring new therapeutic strategies for cancer treatment. Cuproptosis is a novel form of regulatory cell death which is copper-dependent, regulated and distinct from other known cell death regulatory mechanisms. FDX1,LIAS,and DLAT named cuproptosis-related genes play an essential role in regulating cuproptosis. Meanwhile, abnormal accumulation of copper can be observed in various malignant tumors. The correlation has been established between elevated copper levels in serum and tissues and the progression of several cancers. Copper transporters, CTR1 and Copper-transporting ATPases(ATP7A and ATP7B), are mainly involved in regulating the dynamic balance of copper concentration to maintain copper homeostasis. Thus,cuproptosis-related genes and copper transporters will be the focus of cancer research in future. This review elaborated the basic functions of cuproptosis-related genes and copper transporters by retrievalling PubMed. And then we analyzed their potential relationship with cancer aiming to provide theoretical support and reference in cancer progression, diagnosis and treatment for future study.

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Section: Ctr1supporting

confidence: 59%

The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression

Zhao

2023

Front. Oncol.

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“…Among the tested free amino acids here, the concentration of Met and His experienced the major increase at the lethal Cu doses (Table 1 ). These increases could be linked to their ability of binding metal ions to transport them across the cell membrane and to prevent metals entry into the cell (Narayanan and Natarajan 2018 ; Öhrvik and Thiele 2014 ). Combinations of Met/His or Met/Cys can facilitate Cu regulation under different scenarios of pH and redox environments (Rubino et al 2011 ; Rubino and Franz 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Copper toxicity leads to accumulation of free amino acids and polyphenols in Phaeodactylum tricornutum diatoms

Santiago-Díaz

Rivero

Rico

et al. 2023

Environ Sci Pollut Res

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This work is focused on the effect of lethal and sub-lethal copper (Cu) concentrations on the free amino acid and polyphenol production by the marine diatom Phaeodactylum tricornutum (P. tricornutum) after 12, 18, and 21 days of exposure. The concentrations of 10 amino acids (arginine, aspartic acid, glutamic acid, histidine, lysine, methionine, proline, valine, isoleucine, and phenylalanine) and 10 polyphenols (gallic acid, protocatechuic acid, p-coumaric acid, ferulic acid, catechin, vanillic acid, epicatechin syringic acid, rutin, and gentisic acid) were measured by RP-HPLC. Under lethal doses of Cu, free amino acids reached levels significantly higher than those in the control cells (up to 21.9 times higher), where histidine and methionine showed the highest increases (up to 37.4 and 65.8 times higher, respectively). The total phenolic content also increased up to 11.3 and 5.59 times higher compared to the reference cells, showing gallic acid the highest increase (45.8 times greater). The antioxidant activities of cells exposed to Cu were also enhanced with increasing doses of Cu(II). They were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging ability (RSA), cupric ion reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays. Malonaldehyde (MDA) exhibited the same tendency: cells grown at the highest lethal Cu concentration yielded the highest MDA level. These findings reflect the involvement of amino acids and polyphenols in protective mechanisms to overcome the toxicity of copper in marine microalgae. Graphical Abstract

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“…Cuproptosis characterizes a newly recognized mitochondrial cell death caused by intracellular copper accumulation [ 38 , 39 ]. Copper's promotion of angiogenesis is achieved through a combination of increased migration and proliferation of endothelial cells, and enhanced synthesis of fibronectin [ 40 ]. Angiogenesis promotes tumor proliferation and metastasis, resulting in poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

A cuproptosis-related lncRNA signature for predicting prognosis and immunotherapy response of lung adenocarcinoma

Yu¹,

Tang²,

Zhang³

et al. 2023

Hereditas

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Background Copper-induced cell death (cuproptosis) is a new regulatory cell death mechanism. Long noncoding RNAs (lncRNAs) are related to tumor immunity and metastasis. However, the correlation of cuproptosis-related lncRNAs with the immunotherapy response and prognosis of lung adenocarcinoma (LUAD) patients is not clear. Methods We obtained the clinical characteristics and transcriptome data from TCGA-LUAD dataset (containing 539 LUAD and 59 paracancerous tissues). By utilizing LASSO-penalized Cox regression analysis, we identified a prognostic signature composed of cuproptosis-related lncRNAs. This signature was then utilized to segregate patients into two different risk categories based on their respective risk scores. The identification of differentially expressed genes (DEGs) between high- and low-risk groups was carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We evaluated the immunotherapy response by analyzing tumor mutational burden (TMB), immunocyte infiltration and Tumor Immune Dysfunction and Exclusion (TIDE) web application. The "pRRophetic" R package was utilized to conduct further screening of potential therapeutic drugs for their sensitivity. Results We ultimately identified a prognostic risk signature that includes six cuproptosis-related lncRNAs (AP003778.1, AC011611.2, CRNDE, AL162632.3, LY86-AS1, and AC090948.1). Compared with clinical characteristics, the signature was significantly correlated with prognosis following the control of confounding variables (HR = 2.287, 95% CI = 1.648–3.174, p ˂ 0.001), and correctly predicted 1-, 2-, and 3-year overall survival (OS) rates (AUC value = 0.725, 0.715, and 0.662, respectively) in LUAD patients. In terms of prognosis, patients categorized as low risk exhibited more positive results in comparison to those in the high-risk group. The enrichment analysis showed that the two groups had different immune signaling pathways. Immunotherapy may offer a more appropriate treatment option for high-risk patients due to their higher TMB and lower TIDE scores. The higher risk score may demonstrate increased sensitivity to bexarotene, cisplatin, epothilone B, and vinorelbine. Conclusions Based on cuproptosis-related lncRNAs, we constructed and validated a novel risk signature that may be used to predict immunotherapy efficacy and prognosis in LUAD patients.

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Peptides derived from histidine and methionine‐rich regions of copper transporter 1 exhibit anti‐angiogenic property by chelating extracellular Cu

Cited by 10 publications

References 41 publications

The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression

The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression

Copper toxicity leads to accumulation of free amino acids and polyphenols in Phaeodactylum tricornutum diatoms

A cuproptosis-related lncRNA signature for predicting prognosis and immunotherapy response of lung adenocarcinoma

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