NANOGP8 is a retrogene expressed in cancers

Zhang, Jingyu; Wang, Xia; Li, Meixiang; Han, Jin Soo; Chen, Bing; Wang, Bin; Dai, Jianwu

doi:10.1111/j.1742-4658.2006.05186.x

Cited by 111 publications

(112 citation statements)

References 27 publications

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“…In fact, NANOGP8 expression is detected in a number of tumor cells, and it has also been closely associated with cell proliferation (92). The question of whether NANOGP8 plays a role in epithelial tumor progression is currently under investigation in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

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Hyaluronan-CD44 Interaction Activates Stem Cell Marker Nanog, Stat-3-mediated MDR1 Gene Expression, and Ankyrin-regulated Multidrug Efflux in Breast and Ovarian Tumor Cells

Bourguignon¹,

Peyrollier²,

Xia³

et al. 2008

Journal of Biological Chemistry

405

390

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Hyaluronan (HA) is a major glycosaminoglycan in the extracellular matrix whose expression is tightly linked to multidrug resistance and tumor progression. In this study we investigated HA-induced interaction between CD44 (a HA receptor) and Nanog (an embryonic stem cell transcription factor) in both human breast tumor cells (MCF-7 cells) and human ovarian tumor cells (SK-OV-3.ipl cells). Using a specific primer pair to amplify Nanog by reverse transcriptase-PCR, we detected the expression of Nanog transcript in both tumor cell lines. In addition, our results reveal that HA binding to these tumor cells promotes Nanog protein association with CD44 followed by Nanog activation and the expression of pluripotent stem cell regulators (e.g. Rex1 and Sox2). Nanog also forms a complex with the "signal transducer and activator of transcription protein 3" (Stat-3) in the nucleus leading to Stat-3-specific transcriptional activation and multidrug transporter, MDR1 (P-glycoprotein) gene expression. Furthermore, we observed that HA-CD44 interaction induces ankyrin (a cytoskeletal protein) binding to MDR1 resulting in the efflux of chemotherapeutic drugs (e.g. doxorubicin and paclitaxel (Taxol)) and chemoresistance in these tumor cells. Overexpression of Nanog by transfecting tumor cells with Nanog cDNA stimulates Stat-3 transcriptional activation, MDR1 overexpression, and multidrug resistance. Down regulation of Nanog signaling or ankyrin function (by transfecting tumor cells with Nanog small interfering RNA or ankyrin repeat domain cDNA) not only blocks HA/CD44-mediated tumor cell behaviors but also enhances chemosensitivity. Taken together, these findings suggest that targeting HA/CD44-mediated Nanog-Stat-3 signaling pathways and ankyrin/cytoskeleton function may represent a novel approach to overcome chemotherapy resistance in some breast and ovarian tumor cells displaying stem cell marker properties during tumor progression.Multidrug resistance frequently contributes to the failure of chemotherapeutic drug treatments in patients diagnosed with solid tumors such as breast and ovarian cancers (1). It is now certain that oncogenic signaling and cytoskeleton function are directly involved in chemotherapeutic drug resistance and tumor progression (2-4). A number of studies have aimed at identifying those molecules that are expressed specifically by epithelial tumor cells and correlate with metastatic behavior and chemoresistance. Among such molecules is hyaluronan (HA), 2 a major component in the extracellular matrix (ECM) of most mammalian tissues (5, 6). HA is a nonsulfated, unbranched glycosaminoglycan consisting of the repeating disaccharide units, D-glucuronic acid and N-acetyl-D-glucosamine (5, 6). HA is synthesized by specific HA synthases (6, 7) and digested into various smaller sized molecules by various hyaluronidases (8). It is well known that HA is enriched in many types of tumors (9, 10). In cancer patients, HA concentrations are usually higher in malignant tumors than in corresponding benign or normal tissues. Ac...

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Section: Discussionmentioning

confidence: 99%

“…A recent study shows that among 11 pseudogenes derived from the Nanog gene, NANOGP8 appears to be unique based on its sequence homology with Nanog and its retrogene-like (not pseudogene) properties (92). In fact, NANOGP8 expression is detected in a number of tumor cells, and it has also been closely associated with cell proliferation (92).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan-CD44 Interaction Activates Stem Cell Marker Nanog, Stat-3-mediated MDR1 Gene Expression, and Ankyrin-regulated Multidrug Efflux in Breast and Ovarian Tumor Cells

Bourguignon¹,

Peyrollier²,

Xia³

et al. 2008

Journal of Biological Chemistry

405

390

View full text Add to dashboard Cite

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“…Moreover, we did not observe expression of any of the other pluripotencyassociated genes in MCF7-derived spheres, consistently with the results obtained in human tumours. Despite some reports claiming expression of Oct4 and Nanog in breast carcinoma cell lines, expression of several pseudogenes have been reported for both Oct4 and Nanog (Suo et al, 2005;Zhang et al, 2006;Cantz et al, 2007;Ambady et al, 2010), therefore, particular care must be taken to avoid PCR amplification of those pseudogenes. We base our conclusions in antibodybased assays, thus, looking specifically at the protein level to avoid pseudogene detection.…”

Section: Sox2 Activation In Breast Cancer Stem Cellsmentioning

confidence: 96%

Sox2 expression in breast tumours and activation in breast cancer stem cells

Leis¹,

Eguiara²,

et al. 2011

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The cancer stem cell (CSC) model does not imply that tumours are generated from transformed tissue stem cells. The target of transformation could be a tissue stem cell, a progenitor cell, or a differentiated cell that acquires selfrenewal ability. The observation that induced pluripotency reprogramming and cancer are related has lead to the speculation that CSCs may arise through a reprogramming-like mechanism. Expression of pluripotency genes (Oct4, Nanog and Sox2) was tested in breast tumours by immunohistochemistry and it was found that Sox2 is expressed in early stage breast tumours. However, expression of Oct4 or Nanog was not found. Mammosphere formation in culture was used to reveal stem cell properties, where expression of Sox2, but not Oct4 or Nanog, was induced. Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation.

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“…Nanog is a transcription factor that plays a key role in self-renewal and maintenance of pluripotency in human embryonic stem cells. Links to breast cancer include the expression of NANOGP8 in cancer cell lines and cancer tissues 31 and in breast carcinomas.…”

Section: Membrane Protein Profiles Of Tumors That Have Metastasized Tmentioning

confidence: 99%

Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry

et al. 2008

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We have conducted proteome-wide analysis of fresh surgery specimens derived from breast cancer patients, using an approach that integrates size-based intact protein fractionation, nanoscale liquid separation of peptides, electrospray ion trap mass spectrometry, and bioinformatics. Through this approach, we have acquired a large amount of peptide fragmentation spectra from size-resolved fractions of the proteomes of several breast tumors, tissue peripheral to the tumor, and samples from patients undergoing noncancer surgery. Label-free quantitation was used to generate protein abundance maps for each proteome and perform comparative analyses. The mass spectrometry data revealed distinct qualitative and quantitative patterns distinguishing the tumors from healthy tissue as well as differences between metastatic and non-metastatic human breast cancers including many established and potential novel candidate protein biomarkers. Selected proteins were evaluated by Western blotting using tumors grouped according to histological grade, size, and receptor expression but differing in nodal status. Immunohistochemical analysis of a wide panel of breast tumors was conducted to assess expression in different types of breast cancers and the cellular distribution of the candidate proteins. These experiments provided further insights and an independent validation of the data obtained by mass spectrometry and revealed the potential of this approach for establishing multimodal markers for early metastasis, therapy outcomes, prognosis, and diagnosis in the future.

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NANOGP8 is a retrogene expressed in cancers

Cited by 111 publications

References 27 publications

Hyaluronan-CD44 Interaction Activates Stem Cell Marker Nanog, Stat-3-mediated MDR1 Gene Expression, and Ankyrin-regulated Multidrug Efflux in Breast and Ovarian Tumor Cells

Hyaluronan-CD44 Interaction Activates Stem Cell Marker Nanog, Stat-3-mediated MDR1 Gene Expression, and Ankyrin-regulated Multidrug Efflux in Breast and Ovarian Tumor Cells

Sox2 expression in breast tumours and activation in breast cancer stem cells

Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry

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