COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma

Yang, Mi; Wu, Xixi; Hu, Jinlong; Wang, Yingqiao; Wang, Yin; Zhang, Longshan; Huang, Weiqiang; Wang, Xiaoqing; Li, Nan; Liao, Lili; Chen, Min; Xiao, Nanjie; Dai, Yongmei; Liang, Huazhen; Huang, Wenqi; Lü, Yuan; Pan, Hua; Lu, Li; Chen, Longhua; Liu, Laiyu; Li, Liang; Guan, Jian

doi:10.1016/j.jhep.2022.01.009

Cited by 110 publications

(74 citation statements)

References 44 publications

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“…Nevertheless, CuPRiX appears to be a strong candidate as an anti-migratory agent. Recently, Yan, We, Hu et al identified a novel role of copper in promoting the radioresistance of hepatocellular carcinoma cells [53]. We can hypothesize that a synergistic effect of metallic nanoparticles and copper chelation could be obtained in cell lines or tumors with a significantly elevated copper amount.…”

Section: Discussionmentioning

confidence: 96%

A New Generation of Ultrasmall Nanoparticles Inducing Sensitization to Irradiation and Copper Depletion to Overcome Radioresistant and Invasive Cancers

et al. 2022

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An emerging target to overcome cancer resistance to treatments is copper, which is upregulated in a wide variety of tumors and may be associated with cancer progression and metastases. The aim of this study was to develop a multimodal ultrasmall nanoparticle, CuPRiX, based on the clinical AGuIX nanoparticle made of the polysiloxane matrix on which gadolinium chelates are grafted. Such hybrid nanoparticles allow: (i) a localized depletion of copper in tumors to prevent tumor cell dissemination and metastasis formation and (ii) an increased sensitivity of the tumor to radiotherapy (RT) due to the presence of high Z gadolinium (Gd) atoms. CuPRiX nanoparticles are obtained by controlled acidification of AGuIX nanoparticles. They were evaluated in vitro on two cancer cell lines (lung and head and neck) using the scratch-wound assay and clonogenic cell survival assay. They were able to reduce cell migration and invasion and displayed radiosensitizing properties.

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Section: Discussionmentioning

confidence: 96%

A New Generation of Ultrasmall Nanoparticles Inducing Sensitization to Irradiation and Copper Depletion to Overcome Radioresistant and Invasive Cancers

et al. 2022

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“…A recent study showed that radioresistance in HCC may be associated with Cu-Fe homeostasis involved in SLC7A11. Radiotherapy could induce Cu accumulation, inhibit the ubiquitin degradation of HIFα, and promote the transcription of SLC7A11, inhibiting ferroptosis [156].…”

Section: Antioxidant Function and Ferroptosismentioning

confidence: 99%

The Role of SLC7A11 in Cancer: Friend or Foe?

Sun

et al. 2022

Cancers

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SLC7A11 controls the uptake of extracellular cystine in exchange for glutamate at a ratio of 1:1, and it is overexpressed in a variety of tumours. Accumulating evidence has shown that the expression of SLC7A11 is fine-tuned at multiple levels, and plays diverse functional and pharmacological roles in tumours, such as cellular redox homeostasis, cell growth and death, and cell metabolism. Many reports have suggested that the inhibition of SLC7A11 expression and activity is favourable for tumour therapy; thus, SLC7A11 is regarded as a potential therapeutic target. However, emerging evidence also suggests that on some occasions, the inhibition of SLC7A11 is beneficial to the survival of cancer cells, and confers the development of drug resistance. In this review, we first briefly introduce the biological properties of SLC7A11, including its structure and physiological functions, and further summarise its regulatory network and potential regulators. Then, focusing on its role in cancer, we describe the relationships of SLC7A11 with tumourigenesis, survival, proliferation, metastasis, and therapeutic resistance in more detail. Finally, since SLC7A11 has been linked to cancer through multiple approaches, we propose that its contribution and regulatory mechanism require further elucidation. Thus, more personalised therapeutic strategies should be adapted when targeting SLC7A11.

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“…In addition, high intracellular copper concentrations elevated CP expression to reduce intracellular concentrations of Fe, decreasing ferroptosis by directly reducing high levels of lipid peroxidation. Upregulation of CP could also enhance HIF1a expression, forming a HIF1a/CP positive feedback regulatory loop [ 35 ]. DSF/Cu could intensively impair mitochondrial homeostasis, increase free iron pool, also induce p53 protein expression leading to SAT1 and ALOX15 upregulation, enhance lipid peroxidation, and eventually result in ferroptosis.…”

Section: Copper Metabolismmentioning

confidence: 99%

Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD)

Ren

Bai

et al. 2022

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a multistep regulated cell death process induced by iron accumulation and lipid peroxidation. Classical GPX4-dependent pathway and GPX4-independent pathways can independently and synergistically inhibit ferroptosis and jointly maintain the oxidative balance of the body. WHO defines obesity as “a condition of abnormal or excessive fat accumulation in adipose tissue, to the extent that health may be impaired,” and obesity is also defined as an adiposity-based chronic disease (ABCD). Obesity is a systemic disease that leads to metabolic abnormalities in various systems, resulting in a series of complications including obesity cardiomyopathy, atherosclerosis, nonalcoholic fatty liver disease, and diabetes mellitus. Emerging evidence shows that ferroptosis is closely associated with the occurrence and progression of various diseases. In recent years, ferroptosis has been found to play critical roles in obesity and its complications. This review discusses the mechanisms of how ferroptosis is initiated and controlled and discusses the research progress of ferroptosis in obesity and its complications.

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COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma

Cited by 110 publications

References 44 publications

A New Generation of Ultrasmall Nanoparticles Inducing Sensitization to Irradiation and Copper Depletion to Overcome Radioresistant and Invasive Cancers

A New Generation of Ultrasmall Nanoparticles Inducing Sensitization to Irradiation and Copper Depletion to Overcome Radioresistant and Invasive Cancers

The Role of SLC7A11 in Cancer: Friend or Foe?

Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD)

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