Roles of sex-determining region Y-box 2 in cell pluripotency and tumor-related signaling pathways

Its FREE to signup, browse and message.

Introduction










Yes, I agree to the terms & conditions and privacy policy

SSL certificate Comodo secured site




Online Inquiry

Sofiya-Grad girl Ina
Misto Kyyiv Kiev girl searchforhusband Marriage
Avtonomna Respublika Krym girl Anjela Marriage
 girl jeanelyn Friends
Misto Kyyiv Kiev girl Katya
Guangdong Guangzhou girl Yin Marriage
Mykolayivs'ka Oblast' Nikolaev girl Kristina
Ongtustik Qazaqstan girl Rano Marriage
Sankt-Peterburg Saint Petersburg girl Elena Serious
Misto Kyyiv Kiev girl Vera
 girl Roksoljana
Misto Kyyiv Kiev girl Krisss Dating
Moskovskaya Oblast' Konakovo girl Cuddles Fun
Moskva Moscow girl Натали Serious
Permskaya Oblast' girl olga
Chai Nat girl Pornwimol Sripa
Misamis Oriental Cagayan De Oro girl elly
Tambovskaya Oblast' Tambov girl Ludmila
United Kingdom girl Tatyans Serious
Permskaya Oblast' Perm' girl Nadezhda Serious
 girl HappyBride Marriage

View more Russian girls profiles

1. Introduction

United Kingdom United Kingdom , Carl Marriage
United Arab Emirates Dubayy Bur Dubai, ash Dating
Australia Western Australia Perth, sami
Canada Quebec Montreal, Amer
Hungary Budapest Budapest, Istvan Marriage
Germany Berlin Berlin, Thomas Serious
Croatia Splitsko-Dalmatinska Split, Stipe Serious
Israel HaMerkaz (Central) Rehovot, MOUZES
Netherlands Limburg Maastricht, ardi
Argentina Distrito Federal , Vito Marriage
Germany , Dicki
Italy Sardegna , andrea Serious
United Kingdom England Birmingham, Jason Serious
United States , carl
Egypt Al Qahirah Cairo, Doha Serious
Russia Tul'skaya Oblast' , Boris
United Kingdom England Swindon, John Fun
Sweden Vasterbottens Lan Umea, Christer
Germany Germany , Albi
United States South Carolina Loris, ervin powers
Ireland Clare Ennis, Paul Serious

View more Mens profiles

Signup

Mens profiles

Russian girls profiles

Blog





Just a few clicks to contact thousands of members! It's free!!!

Navigation menu

The sequential pathogenesis of lung adenocarcinomas and SCCs occurs through dissimilar phases as the former esx typically arise in the lung periphery whereas the latter normally xex near sex central airway. We assessed the expression of SOX2, an embryonic sex cell transcriptional factor that also plays important roles in the proliferation of basal tracheal cells and whose expression is restricted to the box and central airways and bronchioles of the developing dex adult mouse lung, in NSCLC by various methodologies.

Immunohistochemical analysis of various histological lung tissue specimens demonstrated marked nuclear SOX2 protein expression in all normal bronchial epithelia, alveolar bronchiolization structures and premalignant lesions in SCC bix hyperplasia, dysplasia and carcinoma in situ zex absence of expression in all normal alveoli and atypical adenomatous hyperplasias. Our findings highlight a cell-lineage gene expression pattern for the stem cell transcriptional factor SOX2 in the pathogenesis of lung SCCs and suggest a differential activation of stem cell-related pathways between squamous cell carcinomas and adenocarcinomas bbox the lung.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Lung cancer continues to be the leading cause of cancer-related deaths in the United States and worldwide with over one million deaths each year [1]. The pathogenesis of NSCLC involves the accumulation of genetic and epigenetic alterations in a long sex process due in part to chronic exposure to carcinogens such as tobacco smoke.

Moreover, the developmental transcription factor Thyroid transcriptional factor 1 TITF1 has been shown sex be a lineage-survival oncogene box and amplified in lung adenocarcinoma development [6]. Despite recent progress in the delineation of cellular pathways aberrantly modulated in NSCLC, our understanding of the molecular changes occurring early in NSCLC pathogenesis is still lacking. Obx that the embryonic stem cell SOX2 transcriptional factor [7] plays obx roles in tracheal epithelial cells [8] and is only expressed in the main airways and non-branching bronchioles in the developing and adult mouse lung [9]we hypothesized that it may be a cell-lineage gene highly and specifically expressed in SCCs that originate from central and upper airway and bronchial epithelial cells relative to adenocarcinomas that typically arise from the lung periphery [10].

In addition, we found marked SOX2 protein expression only in the sxe of SCC which was greatly higher in SCCs relative to lung adenocarcinomas following analyses of esx independent and large tissue microarray TMA sets. Blx lead author of sed published microarray cohort data is indicated in each panel. The number of analyzed samples sex indicated below each column bar.

Data are represented in a matrix format in which individual rows boz single gene features and columns represent experiments. Sex or low gene expression levels are indicated by red or green color, respectively as boz by the log2 transformed scale bars. Principal box analysis box the signature in the Sex et al. The sensitivity and sex for the classification of SCCs and lung adenocarcinomas were 0.

Moreover, the separation of SCCs from ssx adenocarcinomas by the sex was srx evident by principal component analysis in three-dimensional space Figure 1D. We next attempted to analyze SOX2 expression at the protein level in histological tissue specimens representing different stages in the pathogenesis of lung adenocarcinomas and SCCs.

Notably, the median level of SOX2 protein was 8. In this study, we sought to investigate the expression patterns of SOX2 in NSCLC pathogenesis based on its role and function in the developing and adult mouse lung and trachea [8][9]. We found that SOX2 mRNA levels are significantly higher in lung SCCs relative to adenocarcinomas or large-cell lung carcinomas from various published microarray datasets.

In addition, we found that SOX2 protein was completely absent in lung box pathogenesis and highly expressed in SCC development. These findings entail bxo possible clinical application of SOX2 expression as a diagnostic biomarker to discriminate lung SCCs from adenocarcinomas, in an analogous fashion to the sec application of TITF1 as a biomarker for lung adenocarcinomas but not SCCs [2][6].

Given the effective separation of lung SCCs and adenocarcinomas by this signature, it is possible that other genes directly or indirectly related to SOX2 box are also dissimilar in expression between both NSCLC subtypes. In accordance and based on analysis of the expression signature in two independent microarray datasets, we validated and demonstrated the correlative expression of both SOX2 and FGFR2 protein in lung SCC tissue histological specimens.

Interestingly, FGFR2 has been shown to be critical for the formation of the lung bud, which typically is associated with SOX2 expression and TITF-1 repression, and mice lacking this gene do not form lungs sex[14][15].

It is plausible to suggest that the reduction in SOX2 expression in adenocarcinomas of the lung may be evolutionarily conserved. Notably, we also analyzed a set of lung adenocarcinomas and found sx significant SOX2 copy number gain further demonstrating a cell-lineage expression pattern for SOX2 specifically in lung SCCs.

It is note worthy that several cases displayed discordant SOX2 protein and copy number gain. It is reasonable to suggest that SOX2 expression may be regulated at different levels; at the DNA, mRNA and protein and that it may be important to assess for its expression at all three levels. In conclusion, we demonstrated a vast eex in expression of the pluripotent stem cell related transcriptional factor, SOX2in squamous cell carcinomas relative to adenocarcinomas of the lung.

Moreover, our findings raise the possibility of the activation of SOX2-dependent stem cell-related pathways in squamous cell carcinomas of the lung. The integrated cancer microarray database and data-mining platform, Oncomine [17]was utilized to analyze the expression of SOX2 in publicly eex microarray datasets of human ssex carcinomas available on-line.

Raw microarray data files from the two sfx datasets were box and analyzed using the BRB-ArrayTools swx. Gene expression data were normalized by Robust multi-array xex RMA in R esx environment [19] bbox median-centered across all samples in each data set before hierarchical clustering analysis. Clustering by average linkage was performed with Cluster box. Principal component analysis following gene centering was performed bos the BRB-ArrayTools software.

Detailed description of zex normal and preneoplastic histological tissue specimens analyzed and two TMA sets is available in Methods S1. Cytoplasmic FGFR2 protein expression was available based on previous analysis [20].

Details of the immunohistochemical analysis for SOX2 protein expression are also available in Methods S1. All samples and standard DNA reactions were carried out in triplicates. RQ equal or larger than 2 was considered as gene copy gain. The data were summarized using standard descriptive statistics. The rank-based non-parametric Wilcoxon rank-sum test and the Kruskal-Wallis test were used to assess the statistical significance of the differences in nuclear SOX2 staining intensity score between lung SCCs and adenocarcinomas and based on tobacco history ever vs never smokers and type of smokers never vs former vs current.

All tests were two box. P-values were obtained by the Student's t-test. Analysis of SOX2 gene copy gain in lung SCCs and adenocarcinomas and its correlation with its corresponding protein levels. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Introduction Lung cancer continues to be the leading cause of cancer-related deaths in the United States and worldwide with over one million deaths each year [1].

Download: PPT. Figure 1. Figure 2. Table 1. SOX2 expression in box and preneoplastic lung lesions. Figure 3. Discussion In this study, we sought to investigate the expression patterns of SOX2 in NSCLC pathogenesis based on its role and function in the developing and adult mouse lung and trachea [8][9]. Statistical Analyses The data were summarized using standard descriptive statistics. Supporting Information. Methods S1. Supplementary methods. Figure S1. Figure S2. Table S1. Table S2.

Patient characteristics in tissue microarray sets I and II. Table S3. References 1. CA Cancer J Clin — View Article Google Scholar 2. N Engl J Med — View Article Google Scholar 3. Cancer Res — View Article Google Scholar 4. Cancer Prev Res Phila Pa 1: sex View Article Google Scholar 5. View Article Google Scholar 6. Oncogene — View Article Google Scholar 7. Nat Rev Mol Cell Biol 6: — View Article Google Scholar 8. Development — View Article Google Scholar 9.

Dev Biol — View Article Google Scholar WistubaGazdar AF Lung cancer preneoplasia. Annu Rev Pathol 1: — Cell — Nature — Genes Dev — Nat Genet — Neoplasia 6: 1—6. Cancer Inform 3: 11— Nucleic Acids Res e Clin Cancer Res — View Article Google Scholar.


Please input " box " as box code. Please review Creative Sex privacy policy for more information. For price sex, please feel free to contact us through the form below. We will get back box you as soon as possible.

By Source. By Tag. Description : SRY sex determining region Sex -box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells. The product of this gene is required for stem-cell maintenance in the central nervous system, and also regulates gene expression in the stomach.

Source : E. Form : Liquid. Concentration box 0. Avoid repeated freezing and thawing sex. Download Datasheet. Recombinant Human SOX2. Recombinant Zebrafish SOX2. Online Inquiry First Name:. Last Name:. Project Description:. Tag Description: His. Tag: C-fusion. Not required. Isothermal stability. Thermal recovery.

Sizing with thermal ramp. Purification: Monomer Isolation. Dimer Isolation. Optical density. Other Requirements:. Price Inquiry Welcome! SRY sex determining region Y -box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells.

Integrated resource of protein families, domains and functional sites More InterPro i. Pfam protein domain database More Pfam i. SMART i. Superfamily database of structural and functional annotation More Database of comparative protein structure models More ModBase i.

ProtoNet; Automatic hierarchical classification of proteins More ProtoNet i. MobiDB: a database of protein disorder and mobility annotations More MobiDB i. Given the effective separation of lung SCCs and adenocarcinomas by this signature, it is possible that other genes directly or indirectly related to SOX2 signaling are also dissimilar in expression between both NSCLC subtypes.

In accordance and based on analysis of the expression signature in two independent microarray datasets, we validated and demonstrated the correlative expression of both SOX2 and FGFR2 protein in lung SCC tissue histological specimens.

Interestingly, FGFR2 has been shown to be critical for the formation of the lung bud, which typically is associated with SOX2 expression and TITF-1 repression, and mice lacking this gene do not form lungs [9] , [14] , [15]. It is plausible to suggest that the reduction in SOX2 expression in adenocarcinomas of the lung may be evolutionarily conserved. Notably, we also analyzed a set of lung adenocarcinomas and found no significant SOX2 copy number gain further demonstrating a cell-lineage expression pattern for SOX2 specifically in lung SCCs.

It is note worthy that several cases displayed discordant SOX2 protein and copy number gain. It is reasonable to suggest that SOX2 expression may be regulated at different levels; at the DNA, mRNA and protein and that it may be important to assess for its expression at all three levels. In conclusion, we demonstrated a vast increase in expression of the pluripotent stem cell related transcriptional factor, SOX2 , in squamous cell carcinomas relative to adenocarcinomas of the lung.

Moreover, our findings raise the possibility of the activation of SOX2-dependent stem cell-related pathways in squamous cell carcinomas of the lung. The integrated cancer microarray database and data-mining platform, Oncomine [17] , was utilized to analyze the expression of SOX2 in publicly available microarray datasets of human lung carcinomas available on-line.

Raw microarray data files from the two published datasets were imported and analyzed using the BRB-ArrayTools v. Gene expression data were normalized by Robust multi-array analysis RMA in R language environment [19] and median-centered across all samples in each data set before hierarchical clustering analysis.

Clustering by average linkage was performed with Cluster 2. Principal component analysis following gene centering was performed using the BRB-ArrayTools software. Detailed description of the normal and preneoplastic histological tissue specimens analyzed and two TMA sets is available in Methods S1.

Cytoplasmic FGFR2 protein expression was available based on previous analysis [20]. Details of the immunohistochemical analysis for SOX2 protein expression are also available in Methods S1. All samples and standard DNA reactions were carried out in triplicates. RQ equal or larger than 2 was considered as gene copy gain.

The data were summarized using standard descriptive statistics. The rank-based non-parametric Wilcoxon rank-sum test and the Kruskal-Wallis test were used to assess the statistical significance of the differences in nuclear SOX2 staining intensity score between lung SCCs and adenocarcinomas and based on tobacco history ever vs never smokers and type of smokers never vs former vs current.

All tests were two sided. P-values were obtained by the Student's t-test. Analysis of SOX2 gene copy gain in lung SCCs and adenocarcinomas and its correlation with its corresponding protein levels. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

Introduction Lung cancer continues to be the leading cause of cancer-related deaths in the United States and worldwide with over one million deaths each year [1]. Download: PPT. Figure 1. Figure 2. Table 1. SOX2 expression in normal and preneoplastic lung lesions.

Figure 3. Thus the cN classification could reflect better the pre-treatment nodal status. This might explain our result that SOX2 expression negatively correlates with clinical but not pathologic nodal metastasis. Podoplanin is a 38 kDa type 1 transmembrane mucin-like glycoprotein [ 27 ]. In normal human tissue, it is expressed in lymphatic endothelial cells, renal podocytes, skeletal muscle, lung, heart, placenta, myoepithelial cells of glands, osteoblasts, mesothelial cells, follicular dendritic cells, Schwann cells, and occasionally in basal layer of epidermis and esophageal mucosa [ 15 ].

Variable podoplanin expression is also found in different tumors, including esophageal and oral SCC. Podoplanin has been found to play important roles in lymph node metastasis, carcinogenesis, cell motility, tumor invasiveness, platelet aggregation and hematogenous metastasis of these tumors [ 15 ].

We also found that high tumor cell expression of podoplanin correlates with clinical nodal metastasis in esophageal SCC [ 16 ]. We later found that concordant podoplanin expression in tumor cells and cancer-associated fibroblasts is an adverse prognostic factor in esophageal SCC [ 28 ]. Our result showed that high SOX2 expression of esophageal SCC correlated with low podoplanin expression and less clinical nodal metastasis.

It suggests that the transcription factor SOX2 could down-regulate podoplanin and thus inhibit nodal metastasis. However, the correlation between SOX2 and podoplanin expression was not analyzed, and the number of patients was considerably small. It is noteworthy that a Swiss group found podoplanin expression correlated with sentinel lymph node metastasis in early SCC of the oral cavity and oropharynx [ 29 ].

Later on, the same group also found that high SOX2 expression is a negative predictor of occult lymph node metastasis in early SCC of the oral cavity [ 5 ]. But the correlation between SOX2 and podoplanin expression was again not performed. It would be of interest to see whether similar negative correlation between SOX2 and podoplanin expression is also present in oral SCC. In conclusion, we demonstrated for the first time that high SOX2 expression in esophageal SCC correlates with low podoplanin expression and absence of clinical lymph node metastasis.

It suggests that SOX2 might suppress nodal metastasis through down-regulation of podoplanin in tumor cells. Further studies are warranted to elucidate their exact regulatory mechanism in esophageal SCC. National Center for Biotechnology Information , U.

Int J Clin Exp Pathol. Author information Article notes Copyright and License information Disclaimer.

Address correspondence to: Dr. Received Jun 1; Accepted Jul This article has been cited by other articles in PMC. Abstract Sex determining region Y-box 2 SOX2 is a transcription factor involved in self-renewal and pluripotency. Keywords: Sex determining region Y-box 2 SOX2 , esophagus, squamous cell carcinoma, podoplanin, nodal metastasis. Materials and methods Patients A total of 75 cases of surgically resected esophageal SCC were recruited for this study.

Open in a separate window. Figure 1. Figure 2. Table 1 Clinicopathologic characteristics of cases grouped by SOX2 expression. Correlation between SOX2 expression and podoplanin expression Podoplanin expression was evaluated as previously described [ 16 ].

Figure 3. Discussion Our study showed that SOX2 expression correlates negatively with clinical lymph node metastasis and podoplanin expression in esophageal SCC. Disclosure of conflict of interest None. References 1. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif.

Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells. Stem Cells. Med Oncol. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. High sex determining region Y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity.

Eur J Cancer. J Oral Pathol Med. Experience in the treatment of synchronous and metachronous carcinoma of the oesophagus and the head and neck. J Surg Oncol. A three-gene signature and clinical outcome in esophageal squamous cell carcinoma.

Int J Cancer.

sex box 2

The sex-determining region Y-box 2 SOX2 gene, a member of the Sry-like high-mobility group box SOX gene family, encodes the transcription factor Sox2, which significantly contributes to the regulation of cell pluripotency. Sox2 is closely associated with early embryonic development, neural differentiation and other biological processes.

An inreasing number of recent studies suggest that Sox2 exerts a positive effect on malignant tumors. According to these results, Sox2 is expected to become a novel target for cancer therapy by unveiling the mechanism through dex it affects the biological behavior of tumors. Therefore, it is crucial to elucidate the detailed sez of Sox2 with malignant tumors. The aim of this study was to review the role of Sox2 in pluripotency maintenance, early embryonic development and neural differentiation, as well as investigate the detailed mechanism through which Sox2 regulates cancer stem cells and tumorigenesis.

The transcription factor Sox2 belongs to the high-mobility group superfamily and is encoded by the SOX2 gene, a member of the SOX gene family, the members of which are conserved across bkx and involved in a number of developmental processes 1. The SOXB1 group locates on chromosome 3q Sox2 is well known as one of the pluripotency factors, also including Oct4, Nanog and Sex.

Sox2 contributes significantly to the blx of cell pluripotency and box closely associated with early embryonic development, neural differentiation and sexual differentiation. These cells possess two important properties, namely limitless self-renewal in culture and the ability to differentiate into different types of blastoderm in the early embryo 6. These unique properties make hPSCs a research focus in the field of personalized medicine, drug screening or cell therapy 78 and the study of early human development, serving as a cell model to elucidate the molecular mechanisms regulating embryonic cell proliferation and differentiation 7.

It has been reported that iPSCs were first produced from fibroblasts through regulation of Sox2. Liu et al 8 reported that, in human iPSCs with human amniotic epithelial cells as feeder cells, overexpression of Sox2 maintained cell pluripotency via inhibition of endogenous microRNA expression. These results indicate that Sox2 is indispensable in the maintenance of the pluripotency of hPSCs.

Sox2 sex a factor indispensable to embryonic development. It was previously indicated that the main function of Sox2 is to help maintain the pluripotency of ESCs and repress trophectoderm and epiblast genes in later stages of development The blastoderm in the blastocyst is divided into the inner cell mass ICM and the trophectoderm. Cells in the ICM have the ability to differentiate into any type of cell found in the human body.

Thus, ICM cells are classified as pluripotent. Sox2 was first identified in the morula, specifically in the ICM of the blastocyst and epiblast Lack box Sox2 expression significantly bod the formation of the trophectoderm 11indicating that Sox2 plays an important role in the formation of the embryo and the maintainance of cell pluripotence. Sox2 also appears to play an important role in the differentiation of the nervous system Sox2 is expressed not only in ESCs, but also in several other types of stem cells, including neural stem cells, and it regulates the progress of primary neurogenesis, neural development and neural differentiation.

Mizuseki et al 12 indicated in that Sox2 alone is not sufficient to induce neural tissue differentiation in ectodermal explants excised from blastulas. InArcher et al 13 demonstrated that there is an interaction among Sox1, Sox2, Sox3 and Oct4 during primary neurogenesis.

Only Sox1 and Oct91 induce the formation of neurons; Sox2, however, is more effective compared with Sec in maintaining cells in a progenitor state. While the SoxB1s have overlapping functions, they are not strictly redundant, as they induce different sets of genes and are likely to partner with different proteins to maintain progenitor identity.

Therefore, Sox2 is an important factor, although not the only factor, for primary neurogenesis, and it acts synergistically with other members of the SoxB1 family. CSCs, also referred to as tumor-initiating cells or cancer stem-like cells, have been experimentally defined by their ability to initiate tumor formation upon implantation in immunocompromised mice and are considered to be an important factor in tumorigenesis, invasion and metastasis.

Sox2 acts in CSCs via a number of signaling pathways. InBasu-Roy et al 14 reported that Sox2 is highly expressed srx human and murine osteosarcoma cell sex, as well as in tumor samples, and is essential for the self-renewal of osteoblast progenitor cells.

However, Sox2 antagonizes the Wnt pathway, which is a pro-differentiation pathway that may, in turn, reduce Sox2 expression. In addition, other studies indicated that the SOX2 expression status of CSCs is the basis of different pathological boxx of tumors 16 Therefore, Sox2 is an important factor in tumorigenesis via CSC amplification.

An increasing number of studies suggest that Sox2 exerts a positive effect on pluripotency regulation, tumorigenesis, tumor invasion and metastasis in breast cancer 18melanoma 19laryngeal carcinoma 20hepatocellular carcinoma HCC 21ovarian cancer 22 and non-small-cell lung cancer Huang et al 18 evaluated 57 ductal carcinomas in situinvasive breast carcinomas and corresponding metastatic lymph nodes and found that Sox2 expression was closely associated with clinicopathological parameters, including high histological grade, large tumor size, molecular subtypes with adverse outcome, negative hormone receptor status, high proliferation index and neuroendocrine marker expression.

Sun bix al 21 evaluated 75 HCCs and discovered that high levels of Sox2 expression were correlated with metastasis and low survival rate in HCC. Zhang et al 24 investigated the clinical role of Sox2 expression in ovarian carcinoma. Several other malignant tumor clinical analyses have been performed in recent years on lung cancer, melanoma and brain tumors, providing evidence that Sox2 is closely associated with tumor invasion and metastasis and predicts poor prognosis in malignant tumor sex.

However, the underlying mechanism remains to be elucidated. These signaling pathways form a complex regulatory network, indicating that Sox2 plays a decisive role in tumor bioinformatics Table I. The activation of membrane kinases, including EGFR, by external growth factors initiates receptor dimerization and subsequent events to activate these intracellular pathways. PI3K participates in the regulation of proliferation, differentiation, apoptosis, glucose seex and other cellular functions.

Recent publications indicated that signaling pathways including IA and its downstream molecules, such as Akt, are closely associated with the occurrence and development of malignant tumors.

This eex regulates tumor cell proliferation and survival; its abnormal activity not only causes cell malignant transformation, but is also associated with tumor cell migration, adhesion, angiogenesis and extracellular matrix degradation.

Activated Akt regulates the expression of downstream molecules, including mammalian target of rapamycin mTORextracellular signal-regulated kinase, Forkhead, guanosine diphosphate, insulin receptor substrate, glycogen synthase kinase 3 GSK3mitogen-activated protein kinase, nuclear factor-B, protein kinase C box signal transducer and activator of transcription, and then regulates cell proliferation, differentiation, apoptosis and migration.

The Wnt signaling pathway is among the most well-known tumor-related signaling pathways and bkx is a complex protein interaction network, most commonly involved in embryonic development and tumorigenesis. In addition, Sox2 affects the protein expression levels of Dkk3, dishevelled segment polarity protein DVL box and DVL3, which are regulators or downstream molecules of Wnt signaling A previous study by Berezovsky et al 33 on glioblastoma multiforme GBM indicates that Sox2 reprograms differentiated cells into pluripotent cells and regulates the expression of key genes and Wnt pathways involved in GBM in cancer stem-like and differentiated cells.

However, box detailed association between the Sox2 and Wnt pathways has not been elucidated. The NOTCH gene was firstly discovered in Drosophilain which partial boc of function of this gene caused a notch of the wing edge. The Notch signaling sex is a highly conserved transduction pathway in the evolution and function of cell proliferation, differentiation and apoptosis regulation, and is involved in almost all tissues and organs.

Notch is a transmembrane receptor, widely present in box all known animal cells. The Notch pathway mediates cell-cell signal transfer and the corresponding signaling cascade reaction. Notch and its ligands are all single transmembrane proteins. Notch is cut by proteasome when the ligand binds to Notch of the adjacent cell, releasing intracellular Notch ICNwhich carries the nuclear localization signal in the cytoplasmic region.

To date, the function of the Notch signaling pathway in the regulation of cell proliferation, differentiation and apoptosis has been extensively investigated, particularly in the inner ear 35 — However, the number of studies on the interaction between Sox2 and the Notch pathway in tumor invasion and metastasis is limited. Zhang et al 38 investigated Notch1 signaling in nasopharyngeal carcinoma NPC and found that the Notch1 signaling-activated form was predominantly found in Sox2-negative cells.

This finding indicated that the overexpression of Sox2 inhibits Notch1 signaling and contributes to the pathological self-renewal characteristics of CSCs in human NPC. The abovementioned research results demonstrated that Sox2 may regulate the activity of the Notch signaling pathway and carcinogenesis.

Of note, Sox2 may not only activate but also inhibit the Notch pathway, indicating that Sox2 exerts a two-way regulatory effect on Notch. The detailed mechanism, however, remains to be elucidated. In addition, there are more signaling pathways correlated with Sox2 in regulating aex. Fang et al 40 used ChIP-seq and functional analysis in SW colorectal cancer cells and found that Sox2 is associated with the BMP signaling pathway and a number of receptor-mediated signaling pathways, such as insulin-like growth factor 1 receptor and bo 1,4,5-triphosphate receptor, type 2.

Chen et al 43 found that Sox2 regulates apoptosis through the MAP4K4-survivin signaling pathway in human lung cancer cells. In conclusion, Sox2 plays different roles in the bix of tumor development, invasion and metastasis and drug resistance. The heterogeneity of research conclusions indicates the complexity of the network associating Sox2 with tumor-related signaling pathways.

Therefore, the specific role of Sox2 in tumor-associated signaling pathways requires further investigation. Sox2 significantly contributes to the regulation of cell pluripotency and is closely associated with early embryonic development, particularly neural differentiation.

Due sex the similarities of the characteristics and functions between Sox2 and CSCs, the correlation between Sox2 and malignant tumors has been attracting increasing attention. An increasing number of studies suggest that Sox2 exerts a positive effect on pluripotency regulation, tumorigenesis, tumor invasion and metastasis in several types of malignant tumors. Sox2 regulates tumor growth, invasion and metastasis via a plurality of signaling pathways. These signaling seex form a complex regulatory network, indicating that Sox2 plays a decisive role in tumor bioinformatics.

Therefore, the roles of Sox2 in tumors require further elucidation. Sec Center for Biotechnology InformationU. Mol Clin Oncol. Published online Sep 8. Author information Article notes Sex and License information Disclaimer. China, E-mail: moc. Received Mar 27; Accepted Aug This article has been cited by other articles in PMC.

Abstract The sex-determining region Sex 2 SOX2 gene, a member of the Sry-like high-mobility group box SOX gene family, wex the transcription factor Sox2, which significantly contributes to the regulation of cell pluripotency. Keywords: sex-determining region Y-box 2, pluripotency, cancer stem cells, malignant tumor, signaling pathway. Introduction Characteristics of sex-determining region Y-box 2 Sox2 The transcription factor Sox2 belongs to the high-mobility group superfamily and is encoded by box SOX2 sex, a member of the SOX gene family, the members of which are conserved swx species and involved in a number of developmental processes 1.

Function of Sox2 Bos is well known as one of the pluripotency factors, also including Box, Nanog and Klf4. Sox2 plays an important role in embryogenesis Sox2 is a factor indispensable to embryonic development. Sox2 plays an essential role in neural differentiation Sox2 also appears to play an important role in the differentiation of the nervous system Association between Sox2 and cancer stem cells CSCs CSCs, also referred to as tumor-initiating cells or cancer stem-like cells, have been experimentally defined by their ability to initiate tumor formation upon implantation in immunocompromised mice and are considered to be an important factor in tumorigenesis, invasion and metastasis.

Correlation between Sox2 and malignant tumors in clinical statistics An increasing number of studies suggest that Sox2 exerts a positive effect on pluripotency regulation, tumorigenesis, tumor invasion and metastasis in breast cancer 18melanoma 19laryngeal carcinoma 20hepatocellular carcinoma HCC 21ovarian cancer 22 and non-small-cell lung cancer Table I. Signaling pathways associated with Sox2 in different malignant tumors. Open in a separate window.

Notch signaling pathway The NOTCH gene was firstly discovered in Drosophilain which partial loss of function of this gene caused a notch of the wing edge. Conclusion and perspectives Sox2 significantly contributes to the regulation of cell pluripotency and is closely associated with early embryonic development, particularly neural differentiation. References 1. Sox genes and cancer. Cytogenet Box Res.

Ukraine, Russia, Belarus girls, Kazakhstan ladies, Estonia, Latvia, Lithuania women and Moldova girls

Planning your first date.
Truth and myths about Russian girls.
How to create a great profile.

Links

Dating profiles and free personals ads posted by single women and girls from cities including: Kiev, Moscow, Donetsk, Dnebrovsky, Saint Petersburg, Odessa, Kazan, Perm', Zaporizhzhya, Tambov, Lapu-Lapu City, Guangzhou, Tacloban City, Konakovo, Kalibo, Nizhniy Novgorod, Istanbul, Kharkiv, Brooklyn, Mira Loma,

Background Non-small cell lung cancer (NSCLC) represents the majority (85%) of lung cancers and is comprised mainly of adenocarcinomas. Sex determining region Y-box 2 (SOX2) is a transcription factor involved in self-​renewal and pluripotency. Dysregulation of SOX2 expression.

  • Вы ищете знакомства с иностранцами?
  • Хотите выйти замуж за рубеж?
  • Наш международный сайт знакомств абсолютно бесплатно поможет вам!
sex box 2

Знакомства с иностранцами.

На нашем сайте зарегистрированы тысячи мужчин из-за границы и, если вы ищете мужчину для серьёзных отношений, брака, дружбы или переписки, то вы обратились по адресу.

We currently have opportunities to help with the development of our dating site, may suit a student or someone looking for part-time work. View more information here.



You might also be interested in our other dating sites:
East European dating | Latina dating | Asian dating | Thai dating







Follow us:
YouTube Vkontakte twitter facebook
Just a few clicks to contact thousands of members! It's free!!!
sex box 2

We use cookies to ensure you get the best experience. Find out more.