<scp>SOX</scp>2 is required to maintain cancer stem cells in ovarian cancer

Wen, Yiping; Hou, Yaya; Huang, Zaiju; Cai, Jing; Wang, Zehua

doi:10.1111/cas.13186

Cited by 78 publications

(67 citation statements)

References 45 publications

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“…Expression of transcription factor SOX2 is one of the hallmarks of embryonic stem cells, induced pluripotent stem cells and CSCs. The relationship between the expression of SOX2 and CSCs population was identified in breast cancer[12], lung cancer[15–17], ovarian cancer[18–20], and cervical cancer [21]. In our previous study, SOX2-positive cells isolated from the cervical cancer cell lines SiHa and C33A were found to exhibit self-renewal, differentiation, and tumor initiating properties, which are major characteristics of CSCs[7].…”

Section: Discussionmentioning

confidence: 99%

NF-YA Transcriptionally Activates the Expression of SOX2 in Cervical Cancer Stem Cells

Yang

Zhao

et al. 2019

Preprint

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22Roles for SOX2 have been extensively studied in several types of cancer, 23 including colorectal cancer, glioblastoma and breast cancer, with particular emphasis 24 placed on the roles of SOX2 in cancer stem cell. Our previous study identified SOX2 25 as a marker in cervical cancer stem cells driven by a full promoter element of SOX2 26 EGFP reporter. Here, dual-luciferase reporter and mutagenesis analyses were 27 employed, identifying key cis-elements in the SOX2 promoter, including binding sites 28 for SOX2, OCT4 and NF-YA factors in SOX2 promoter. Mutagenesis analysis 29 provided additional evidence to show that one high affinity-binding domain CCAAT 30 box was precisely recognized and bound by the transcription factor NF-YA. 31 Furthermore, overexpression of NF-YA in primitive cervical cancer cells SiHa and 32 C33A significantly activated the transcription and the protein expression of SOX2. 33 Collectively, our data identified NF-YA box CCAAT as a key cis-element in the 34 SOX2 promoter, suggesting that NF-YA is a potent cellular regulator in the 35 maintenance of SOX2-positive cervical cancer stem cell by specific transcriptional 36 activation of SOX2.37 3 39 4 61 length of SOX2 promoter with 11.5kb nucleotides positioned upstream of the EGFP 62 reporter[7]. However, This plasmid was so large (approximately 16kb) that the 63 transfection efficiency in cervical cancer cell lines was so low for sorting the 64 endogenous SOX2-positive cells. Here, in order to explore the functional domain in 65 the promoter of SOX2 helps us to efficiently capture CSCs and elucidate the role of 66 SOX2, upstream regulatory factor, and related signaling pathways, we try to obtained 67 the trans-factors that specifically bond to the key domain region of SOX2 promoter 68 and activated the expression of SOX2 69 Materials and methods 70 Ethics Statement 71 Investigation has been conducted in accordance with the ethical standards and 72 according to the Declaration of Helsinki and according to national and international 73 guidelines and has been approved by the review board of the First Affiliated Hospital 74 of Xi'an Jiaotong University. 75 Cell lines and culture conditions 76 The human cervical cancer cell lines SiHa and C33A were obtained from the 77 American Type Culture Collection (ATCC; Manassas, VA). SiHa and C33A cells 78 were cultured in Dulbecco's Modified Eagle Medium-high glucose (DMEM; 79 Sigma-Aldrich, St. Louis, MO) supplemented with 10% fetal bovine serum (FBS; 80 Invitrogen, Carlsbad, CA) and maintained at 37°C in an atmosphere containing 5% 81 carbon dioxide.

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Section: Discussionmentioning

confidence: 99%

NF-YA Transcriptionally Activates the Expression of SOX2 in Cervical Cancer Stem Cells

Yang

Zhao

et al. 2019

Preprint

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“…Moreover, transduction of SOX2 into OC cell lines also enhanced resistance to cell apoptosis through overexpression of the anti-apoptotic gene BCL2 and simultaneous down-regulation of the pro-apoptotic genes PUMA/BBC3 and NOXA/PAMAIP1 34 . Overexpression of SOX2 also accelerated cell migration by down-regulating E-cadherin and up-regulating vimentin expression 31 . These results at the cellular level were not as the same as the results based on clinical samples, which suggested that in vitro studies could not imitate the environment in the body completely.…”

Section: Sox Genes In Gcsmentioning

confidence: 93%

“…Knockdown of SOX2 in cell lines accordingly decreased chemoresistance to cisplatin via down-regulating expression of ABCB1 , ABCG2 , and ABCC6 31 . These results were accordance with those of researches on the roles of SOX2 based on OC cell lines, but not with researches based on patients’ samples in other cases 9,31,34,38,39 . Further simultaneous in vitro and in vivo researches into SOX2 are therefore needed to develop its role as a promising new therapeutic target for patients with OC.…”

Section: Sox Genes In Gcsmentioning

confidence: 97%

“…Due to lack of specific symptoms and reliable screening methods, approximately 70% of patients with OC are diagnosed at advanced stage with metastasis beyond the ovary, which contributes to its high mortality 31,32 . Thus, there is an urgent need to find novel diagnostic biomarkers for detecting OC at a premalignant stage 33 .…”

Section: Sox Genes In Gcsmentioning

confidence: 99%

“…Thus, there is an urgent need to find novel diagnostic biomarkers for detecting OC at a premalignant stage 33 . SOX genes are identified as such biomarkers that can contribute to early screening and the prediction of clinical features in patients with OC, and regulation of SOX gene expression could influence cell proliferation and treatment efficacy at the cellular level 9,10,16,18,31,34 . …”

Section: Sox Genes In Gcsmentioning

confidence: 99%

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Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

et al. 2019

Cancer Biol Med

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Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis. Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical, and endometrial cancer. In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels. Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers. An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.

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Sirtuin‐1/Mitochondrial Ribosomal Protein S5 Axis Enhances the Metabolic Flexibility of Liver Cancer Stem Cells

et al. 2019

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Metabolic reprogramming endows cancer cells with the ability to adjust metabolic pathways to support heterogeneously biological processes. However, it is not known how the reprogrammed activities are implemented during differentiation of cancer stem cells (CSCs). In this study, we demonstrated that liver CSCs relied on the enhanced mitochondrial function to maintain stemness properties, which is different from aerobic glycolysis playing main roles in the differentiated non-CSCs. We found that liver CSCs exhibit increased mitochondrial respiratory capacity and that complex-I of mitochondria was necessary for stemness properties of liver CSCs through regulation of mitochondrial respiration. Bioinformatics analysis reveals that mitochondrial ribosomal protein S5 (MRPS5) is closely related with the function of complex-I. Further experiments confirmed that MRPS5 promoted the production of nicotinamide adenine dinucleotide (NAD + ), which is necessary for enhanced mitochondrial function in liver CSCs. MRPS5 played a critical role for liver CSCs to maintain stemness properties and to participate in tumor progression. Mechanistically, the acetylation status of MRPS5 is directly regulated by NAD + dependent deacetylase sirtuin-1 (SIRT1), which is abundant in liverCSCs and decreased during differentiation. Deacetylated MRPS5 locates in mitochondria to promote the function complex-I and the generation of NAD + to enhance mitochondrial respiration. Conversely, the acetylated MRPS5 gathered in nuclei leads to increased expression of glycolytic proteins and promotion of the Warburg Effect. Therefore, liver CSCs transform mitochondrial-dependent energy supply to a Warburg phenotype by the dual function of MRPS5. Clinical analysis of SIRT1 and MRPS5 expression in tumor tissues showed the SIRT1 High /Cytoplasmic-MRPS5 High profile was associated with patients with hepatocellular carcinoma with poor prognosis. Conclusion: SIRT1/MRPS5 axis participates in metabolic reprogramming to facilitate tumor progression and may serve as a promising therapeutic target of liver cancer. (Hepatology 2019;70:1197-1213).

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SOX2 is required to maintain cancer stem cells in ovarian cancer

Cited by 78 publications

References 45 publications

NF-YA Transcriptionally Activates the Expression of SOX2 in Cervical Cancer Stem Cells

NF-YA Transcriptionally Activates the Expression of SOX2 in Cervical Cancer Stem Cells

Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

Sirtuin‐1/Mitochondrial Ribosomal Protein S5 Axis Enhances the Metabolic Flexibility of Liver Cancer Stem Cells

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