RETRACTED ARTICLE: Intracellular citrate accumulation by oxidized ATM-mediated metabolism reprogramming via PFKP and CS enhances hypoxic breast cancer cell invasion and metastasis

Peng, Meixi; Yang, Dan; Hou, Yixuan; Liu, Shuiqing; Zhao, Mingqiu; Qin, Yilu; Chen, Rui; Teng, Yong; Liu, Manran

doi:10.1038/s41419-019-1475-7

Cited by 81 publications

(67 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ubiquitination of enzymes involved in the TCA cycle is also associated with cancer progression. Decreased UBR5-mediated ubiquitination of citrate synthase leads to citrate accumulation in hypoxia breast cancer cells, promoting cell migration, invasion, and metastasis [269]. HIF-1 activation under hypoxia condition can promote α-ketoglutarate dehydrogenase (α-KGDH) complex ubiquitination and proteolysis by SIAH2.…”

Section: Ubiquitination and Metabolic Enzymesmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

View full text Add to dashboard Cite

Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

show abstract

Section: Ubiquitination and Metabolic Enzymesmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

View full text Add to dashboard Cite

show abstract

“…This way, glucose is mainly metabolized in biosynthetic pathways, leaving the bioenergetics role to be played by glutamine. Moreover, citrate synthase (CS) expression is upregulated in cancer upon metabolic stressful conditions such as hypoxia, favoring the metabolic glutamine reliance [ 71 ]. Glutamine is also important in biomass production through the above-mentioned intervention in amino acid synthesis and also as a source for lipids, since citrate and glutamine-originated acetyl-CoA is the most relevant lipid precursor [ 63 , 72 , 73 ], accounting for about 20% of lipogenic acetyl-CoA [ 72 ].…”

Section: Glutamine-glutamate Relevance In Cancermentioning

confidence: 99%

Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

et al. 2020

View full text Add to dashboard Cite

Glutamine is a non-essential amino acid that plays a key role in the metabolism of proliferating cells including neoplastic cells. In the central nervous system (CNS), glutamine metabolism is particularly relevant, because the glutamine-glutamate cycle is a way of controlling the production of glutamate-derived neurotransmitters by tightly regulating the bioavailability of the amino acids in a neuron-astrocyte metabolic symbiosis-dependent manner. Glutamine-related metabolic adjustments have been reported in several CNS malignancies including malignant gliomas that are considered ‘glutamine addicted’. In these tumors, glutamine becomes an essential amino acid preferentially used in energy and biomass production including glutathione (GSH) generation, which is crucial in oxidative stress control. Therefore, in this review, we will highlight the metabolic remodeling that gliomas undergo, focusing on glutamine metabolism. We will address some therapeutic regimens including novel research attempts to target glutamine metabolism and a brief update of diagnosis strategies that take advantage of this altered profile. A better understanding of malignant glioma cell metabolism will help in the identification of new molecular targets and the design of new therapies.

show abstract

“…Breast cancer is characterized by high PFKP expression that, in turn, has been associated with decreased patient survival [6]. Accumulating evidence has demonstrated that PFKP plays a crucial role in promoting aerobic glycolysis and lactate production in breast cancer cells, thereby stimulating cancer cell proliferation and metastasis [7][8]. Deletion of PFKP can signi cantly inhibit lactate production to impair invasion and migration by breast cancer cells [9,10].…”

Section: Introductionmentioning

confidence: 99%

Anti-Warburg effect by targeting HRD1-PFKP pathway may inhibit breast cancer progression

Fan

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Our previous studies have shown that the E3 ubiquitin ligase of HMG-CoA reductase degradation 1 (HRD1) functions as a tumor suppressor, as overexpression of HRD1 suppressed breast cancer proliferation and invasion. However, its role in breast cancer cell glucose metabolism was unclear. Here, our aim was to uncover the role and molecular mechanisms of HRD1 in regulating aerobic glycolysis in breast cancer. Methods: The effect of HRD1 on robic glycolysis in breast cancer cells were assessed. Then the proliferation, colony formation ability, invasion and migration of breast cancer cells were evaluated. The relationship between HRD1 and PFKP was validated by Mass spectrometry analysis, immunofluorescence and co-immunoprecipitation. The level of PFKP ubiquitination was measured using ubiquitylation assay. Furthermore, the tumor growth and metastasis in mice xenografts were observed. Results: We found that upregulation of HRD1 clearly decreased aerobic glycolysis, and subsequently inhibited breast cancer proliferation and invasion. Mass spectrometry analysis results revealed a large HRD1 interactome, which included PFKP (platelet isoform of phosphofructokinase), a critical enzyme involved in the Warburg Effect in breast cancer. Mechanistically, HRD1 interacted and colocalized with PFKP in the cytoplasm, targeted PFKP for ubiquitination and degradation, and ultimately reduced PFKP expression and activity in breast cancer cells. HRD1 inhibited breast cancer growth and metastasis in vivo through a PFKP-dependent wayConclusions: Our findings reveal a new regulatory role of HRD1 in Warburg effect and provide a key contributor in breast cancer metabolism.

show abstract

RETRACTED ARTICLE: Intracellular citrate accumulation by oxidized ATM-mediated metabolism reprogramming via PFKP and CS enhances hypoxic breast cancer cell invasion and metastasis

Cited by 81 publications

References 50 publications

The role of ubiquitination and deubiquitination in cancer metabolism

The role of ubiquitination and deubiquitination in cancer metabolism

Take Advantage of Glutamine Anaplerosis, the Kernel of the Metabolic Rewiring in Malignant Gliomas

Anti-Warburg effect by targeting HRD1-PFKP pathway may inhibit breast cancer progression

Contact Info

Product

Resources

About