Aberrantly elevated redox sensing factor Nrf2 promotes cancer stem cell survival via enhanced transcriptional regulation of ABCG2 and Bcl-2/Bmi-1 genes

Jia, Yan; Chen, Jun; Zhu, He; Jia, Zanhui; Cui, Manhua

doi:10.3892/or.2015.4214

Cited by 62 publications

(38 citation statements)

References 31 publications

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“…Previously, Nrf2 has been shown to induce transcription of heme oxygenase-1 and superoxide dismutase, which can in turn also activate the NLRP3 inflammasome 112. Finally, ABCG2 expression has been shown to be upregulated by Nrf2, which promotes cancer stem cell survival 46. Taken together, ABCG2 plays a role in autophagy and its expression is induced through Nrf2.…”

Section: Abcg2 and Autophagymentioning

confidence: 98%

“…Upstream of HIF-1α, signaling via phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K) and protein B kinase (Akt) regulates ABCG2 expression on the cell membrane 42–45. Furthermore, nuclear factor E2-related factor 2 (Nrf2), a transcription factor involved in activating oxidative stress responses, can induce ABCG2 transcription46 in addition to inducing the expression of peroxisome proliferator-activated receptor gamma (PPARγ) 47,48. Finally, the hormone estrogen has been found to up-regulate ABCG2 gene expression 49–51.…”

Section: Regulation Of Abcg2 Expressionmentioning

confidence: 99%

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ABCG2 polymorphisms in gout: insights into disease susceptibility and treatment approaches

Cleophas¹,

Joosten²,

Stamp³

et al. 2017

PGPM

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As a result of the association of a common polymorphism (rs2231142, Q141K) in the ATP-binding cassette G2 (ABCG2) transporter with serum urate concentration in a genome-wide association study, it was revealed that ABCG2 is an important uric acid transporter. This review discusses the relevance of ABCG2 polymorphisms in gout, possible etiological mechanisms, and treatment approaches. The 141K ABCG2 urate-increasing variant causes instability in the nucleotide-binding domain, leading to decreased surface expression and function. Trafficking of the protein to the cell membrane is altered, and instead, there is an increased ubiquitin-mediated proteasomal degradation of the variant protein as well as sequestration into aggresomes. In humans, this leads to decreased uric acid excretion through both the kidney and the gut with the potential for a subsequent compensatory increase in renal urinary excretion. Not only does the 141K polymorphism in ABCG2 lead to hyperuricemia through renal overload and renal underexcretion, but emerging evidence indicates that it also increases the risk of acute gout in the presence of hyperuricemia, early onset of gout, tophi formation, and a poor response to allopurinol. In addition, there is some evidence that ABCG2 dysfunction may promote renal dysfunction in chronic kidney disease patients, increase systemic inflammatory responses, and decrease cellular autophagic responses to stress. These results suggest multiple benefits in restoring ABCG2 function. It has been shown that decreased ABCG2 141K surface expression and function can be restored with colchicine and other small molecule correctors. However, caution should be exercised in any application of these approaches given the role of surface ABCG2 in drug resistance.

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Section: Abcg2 and Autophagymentioning

confidence: 98%

Section: Regulation Of Abcg2 Expressionmentioning

confidence: 99%

ABCG2 polymorphisms in gout: insights into disease susceptibility and treatment approaches

Cleophas¹,

Joosten²,

Stamp³

et al. 2017

PGPM

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“…It is well known that the BCL2 antiapoptotic family of proteins protects CSCs from apoptosis and enhances their ability to repopulate [117]. BCL2 overexpression in CSCs from several cancers, including prostate and breast cancers, has been found to play a role in chemotherapy resistance [118, 119].…”

Section: Implications Of Stemness For Cancer Therapymentioning

confidence: 99%

Overview of Cancer Stem Cells and Stemness for Community Oncologists

2017

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Advances in cancer research in the past have led to an evolving understanding of cancer pathogenesis and the development of novel drugs that significantly improve patient outcomes. However, many patients still encounter treatment resistance, recurrence, or metastasis and eventually die from progressing disease. Experimental evidence indicates that a subpopulation of cancer cells, called cancer stem cells (CSCs), possess “stemness” properties similar to normal stem cells, including self-renewal, differentiation, and proliferative potential. These stemness properties are lost during differentiation and are governed by pathways such as STAT3, NANOG, NOTCH, WNT, and HEDGEHOG, which are highly dysregulated in CSCs due to genetic and epigenetic changes. Promising results have been observed in preclinical models targeting these CSCs through the disruption of stemness pathways in combination with current treatment modalities. This has led to anti-CSC–based clinical trials in multiple stages of development. In this review, we discuss the role of CSCs and stemness pathways in cancer treatment and how they relate to clinical observations. Because CSCs and the stemness pathways governing them may explain the negative clinical outcomes observed during treatment, it is important for oncologists to understand how they contribute to cancer progression and how they may be targeted to improve patient outcomes.

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“…The expression and activity of ABCG2 may interact with various lipid compounds, especially those residing in close proximity within the plasma membrane [76]. In cervical cancer, the redox sensing factor Nrf2 may play an important role in the transcriptional regulation of ABCG2, and cells with upregulated Nrf2 and ABCG2 exhibit stem-like characters, including infinite cell proliferation, longevity and prevention of apoptosis [77]. Three commercial cell lines, SiHa, CaLo, and C-33A, were sorted using fluorescence-activated cell sorting (FACS) to obtain SP and non-SP (NSP) cells.…”

Section: Abcg2mentioning

confidence: 99%

Cancer stem cells (CSCs), cervical CSCs and targeted therapies

2016

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Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain “purified” CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma.

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Aberrantly elevated redox sensing factor Nrf2 promotes cancer stem cell survival via enhanced transcriptional regulation of ABCG2 and Bcl-2/Bmi-1 genes

Cited by 62 publications

References 31 publications

ABCG2 polymorphisms in gout: insights into disease susceptibility and treatment approaches

ABCG2 polymorphisms in gout: insights into disease susceptibility and treatment approaches

Overview of Cancer Stem Cells and Stemness for Community Oncologists

Cancer stem cells (CSCs), cervical CSCs and targeted therapies

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