Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis

Wang, Zhipeng; Liang, Shuang; Lian, Xin; Liu, Lei; Song, Zhao; Xuan, Qijia; Li, Guo; Liu, Huan; Yang, Yilin; Dong, Tieying; Liu, Yanchen; Liu, Zhaoliang; Zhang, Qingyuan

doi:10.1038/srep09301

Cited by 51 publications

(35 citation statements)

References 57 publications

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“…Moreover, evidence suggested that elevated levels of NADPH and GSH, together with an active PPP, play an important role in MDR2930. Our results together with other recent studies3132 contradict the above-mentioned reports, showing that PPP enzymes are downregulated in MDR cells. These results are controversial since one of the roles of PPP is to provide reducing power to the GSH metabolism and high levels of GSH in tumors have been linked to the development of MDR33.…”

Section: Discussioncontrasting

confidence: 78%

Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles

Lopes-Rodrigues

Luca

Mleczko

et al. 2017

Sci Rep

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Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays a significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations could affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify metabolic alterations in P-gp overexpressing cells that could be involved in the development of MDR and, ii) identify a potential role for the EVs in the acquisition of the MDR. Two different pairs of MDR and their drug-sensitive counterpart cancer cell lines were used. Our results showed that MDR (P-gp overexpressing) cells have a different metabolic profile from their drug-sensitive counterparts, demonstrating decreases in the pentose phosphate pathway and oxidative phosphorylation rate; increases in glutathione metabolism and glycolysis; and alterations in the methionine/S-adenosylmethionine pathway. Remarkably, EVs from MDR cells were capable of stimulating a metabolic switch in the drug-sensitive cancer cells, towards a MDR phenotype. In conclusion, obtained results contribute to the growing knowledge about metabolic alterations in MDR cells and the role of EVs in the intercellular transfer of MDR. The specific metabolic alterations identified in this study may be further developed as targets for overcoming MDR.

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Section: Discussioncontrasting

confidence: 78%

Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles

Lopes-Rodrigues

Luca

Mleczko

et al. 2017

Sci Rep

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“…NRF2-induced GCLM expression up-regulates GSH synthesis and associated Imatinib resistance in chronic leukaemia cells has been reported [24,177] . The enzymes involved in the pentose phosphate pathway (PPP) including glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase 1, malic enzyme 1, transketolase isoform 1 and transaldolase 1 were found to be regulated by NRF2 [178][179][180][181] . Anticancer drug induced NRF2 hyperactivation transcriptionally activates these genes and facilitates PPP.…”

Section: Other Nrf2 Regulated Genes/proteinsmentioning

confidence: 99%

Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies

Paramasivan¹,

Kankia²,

Langdon³

et al. 2019

CDR

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Nuclear factor E2-related factor 2 (NRF2), a transcription factor, is a master regulator of an array of genes related to oxidative and electrophilic stress that promote and maintain redox homeostasis. NRF2 function is well studied in in vitro, animal and general physiology models. However, emerging data has uncovered novel functionality of this transcription factor in human diseases such as cancer, autism, anxiety disorders and diabetes. A key finding in these emerging roles has been its constitutive upregulation in multiple cancers promoting pro-survival phenotypes. The survivability pathways in these studies were mostly explained by classical NRF2 activation involving KEAP-1 relief and transcriptional induction of reactive oxygen species (ROS) neutralizing and cytoprotective drug-metabolizing enzymes (phase I, II, III and 0). Further, NRF2 status and activation is associated with lowered cancer therapeutic efficacy and the eventual emergence of therapeutic resistance. Interestingly, we and others have provided further evidence of direct NRF2 regulation of anticancer drug targets like receptor tyrosine kinases and DNA damage and repair proteins and kinases with implications for therapy outcome. This novel finding demonstrates a renewed role of NRF2 as a key modulatory factor informing anticancer therapeutic outcomes, which extends beyond its described classical role as a ROS regulator. This review will provide a knowledge base for these emerging roles of NRF2 in anticancer therapies involving feedback and feed forward models and will consolidate and present such findings in a systematic manner. This places NRF2 as a key determinant of action, effectiveness and resistance to anticancer therapy.

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“…Some other genes, such as glucose-6-phosphate dehydrogenase (G6PD), isocitrate dehydrogenase 1 (IDH1) (Wang et al, 2015), malic enzyme 1 (ME1) (Cui et al, 2014), transketolase isoform 1 (TKT) and transaldolase 1 (TALDO1) (Basta et al, 2008) are also found to be regulated by NRF2 in human and mouse model (Chartoumpekis et al, 2015). All of them are involved in the pentose phosphate pathway (PPP) that provides energy for cell proliferation.…”

Section: Other Metabolism-related Genes Targeted By Nrf2 In Cancermentioning

confidence: 99%

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Bai

Chen

Hou

et al. 2016

Drug Metabolism Reviews

137

105

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Chemoresistance is a disturbing barrier in cancer therapy, which always results in limited therapeutic options and unfavorable prognosis. Nuclear factor E2-related factor 2 (NRF2) controls the expression of genes encoding cytoprotective enzymes and transporters that protect against oxidative stress and electrophilic injury to maintain intrinsic redox homeostasis. However, recent studies have demonstrated that aberrant activation of NRF2 due to genetic and/or epigenetic mutations in tumor contributes to the high expression of phase I and phase II drug-metabolizing enzymes, phase III transporters, and other cytoprotective proteins, which leads to the decreased therapeutic efficacy of anticancer drugs through biotransformation or extrusion during chemotherapy. Therefore, a better understanding of the role of NRF2 in regulation of these enzymes and transporters in tumors is necessary to find new strategies that improve chemotherapeutic efficacy. In this review, we summarized the recent findings about the chemoresistance-promoting role of NRF2, NRF2-regulated phase I and phase II drug-metabolizing enzymes, phase III drug efflux transporters, and other cytoprotective genes. Most importantly, the potential of NRF2 was proposed to counteract drug resistance in cancer treatment.

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Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis

Cited by 51 publications

References 57 publications

Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles

Identification of the metabolic alterations associated with the multidrug resistant phenotype in cancer and their intercellular transfer mediated by extracellular vesicles

Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

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