Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy

Yang, Shaobo; Zheng, Jicui; Ma, Yangyang; Zhu, Haitao; Xu, Tao; Dong, Ke; Xiao, Xia

doi:10.3892/or.2012.1765

Cited by 19 publications

(13 citation statements)

References 25 publications

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“…Our results show alterations not only in POU5F1 but also in members of TGF-β, Notch and Wnt signalling pathways indicating the potential of this gene to be used as a new therapeutical target. Our findings are supported by other works that described its potential in other tumors [62], [64], [67] and as a possible new CSC marker in neuroblastoma [67]–[69].…”

Section: Discussionsupporting

confidence: 91%

“…POU5F1 was described in several tumors (urothelial, prostatic, cervical, breast and lung) and is implicated in different functions as chemoresistance, prognosis marker, proliferation, apoptosis, migration and invasion [58]–[61]. In addition to all these functions, this gene plays an important role in stemness and self-renewal of stem cells in normal and tumor tissues [60], [62], [63] and was found to be overexpressed and correlated with the progression of neuroblastoma [64]. This gene could interact with members from other pathways as TGF-β, Notch and Wnt [65], [66] working together in the regulation of stem cell pluripotency.…”

Section: Discussionmentioning

confidence: 99%

“…The evidence of possible targets involved in the development and regulation of other tumors could be an approach to develop new strategies in neuroblastoma. A good example are the different pathways involved in tumorigenesis and CSC regulation, as Wnt [62], [64], [67]–[69], Notch [84], Hh [85]–[87] and TGF-β [18], [88], [89]. In this connection, an interesting case are the ion transporters, described as essential for cell proliferation and which appear to have a role in cancer development [90]–[92].…”

Section: Discussionmentioning

confidence: 99%

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Genome-Wide Microarray Expression and Genomic Alterations by Array-CGH Analysis in Neuroblastoma Stem-Like Cells

et al. 2014

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Neuroblastoma has a very diverse clinical behaviour: from spontaneous regression to a very aggressive malignant progression and resistance to chemotherapy. This heterogeneous clinical behaviour might be due to the existence of Cancer Stem Cells (CSC), a subpopulation within the tumor with stem-like cell properties: a significant proliferation capacity, a unique self-renewal capacity, and therefore, a higher ability to form new tumors. We enriched the CSC-like cell population content of two commercial neuroblastoma cell lines by the use of conditioned cell culture media for neurospheres, and compared genomic gains and losses and genome expression by array-CGH and microarray analysis, respectively (in CSC-like versus standard tumor cells culture). Despite the array-CGH did not show significant differences between standard and CSC-like in both analyzed cell lines, the microarray expression analysis highlighted some of the most relevant biological processes and molecular functions that might be responsible for the CSC-like phenotype. Some signalling pathways detected seem to be involved in self-renewal of normal tissues (Wnt, Notch, Hh and TGF-β) and contribute to CSC phenotype. We focused on the aberrant activation of TGF-β and Hh signalling pathways, confirming the inhibition of repressors of TGF-β pathway, as SMAD6 and SMAD7 by RT-qPCR. The analysis of the Sonic Hedgehog pathway showed overexpression of PTCH1, GLI1 and SMO. We found overexpression of CD133 and CD15 in SIMA neurospheres, confirming that this cell line was particularly enriched in stem-like cells. This work shows a cross-talk among different pathways in neuroblastoma and its importance in CSC-like cells.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genome-Wide Microarray Expression and Genomic Alterations by Array-CGH Analysis in Neuroblastoma Stem-Like Cells

et al. 2014

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“…Notably, the BMP4 pathway is involved in mammalian palatogenesis [71], and mutations in BMP4 have been associated with human NSCL/P [12], [58], [59]. Research has shown that OCT4 is overexpressed in cancer cell lines and in diverse cancer entities [24], [37], [67], suggesting that aberrant transcriptional regulation of OCT4 might be a mechanism in cancer susceptibility. Thus, a plausible hypothesis is that rs6457327 regulates OCT4 expression, and that this regulation is a possible common process in oncogenesis and the development of NSCL/P.…”

Section: Discussionmentioning

confidence: 99%

Nonsyndromic cleft lip with or without cleft palate and cancer: Evaluation of a possible common genetic background through the analysis of GWAS data

et al. 2016

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Previous research suggests a genetic overlap between nonsyndromic cleft lip with or without cleft palate (NSCL/P) and cancer. The aim of the present study was to identify common genetic risk loci for NSCL/P and cancer entities that have been reported to co-occur with orofacial clefting. This was achieved through the investigation of large genome-wide association study datasets. Investigations of 12 NSCL/P single nucleotide polymorphisms (SNPs) in 32 cancer datasets, and 204 cancer SNPs in two NSCL/P datasets, were performed. The SNPs rs13041247 (20q12) and rs6457327 (6p21.33) showed suggestive evidence for an association with both NSCL/P and a specific cancer entity. These loci harbor genes of biological relevance to oncogenesis (MAFB and OCT4, respectively). This study is the first to characterize possible pleiotropic risk loci for NSCL/P and cancer in a systematic manner. The data represent a starting point for future research by identifying a genetic link between NSCL/P and cancer.

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“…OCT4-expressing cancer cells show increased tumorigenicity and high resistance to chemotherapeutics (13). The expression of OCT4 is upregulated in neuroblastoma; however, it is inhibited by chemotherapy (14), suggesting that it may be a new target for identifying candidate antitumor drugs. Therefore, OCT4 may be important in carcinogenesis and may provide one possible mechanism by which cancer cells acquire a drug-resistant phenotype (15).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway

Lin

Sun

Han

et al. 2014

Molecular Medicine Reports

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Octamer-binding transcription factor 4 (OCT4) is one of the factors associated with self-renewal and differentiation in cancer stem cells, and is crucial for the progression of various types of human malignancy. However, the expression and function of OCT4 in human pancreatic cancer has not been fully elucidated. The purpose of the present study was to investigate the function and molecular mechanisms of OCT4 in pancreatic cancer cells. The clinical significance of OCT4 expression was assessed by an immunohistochemical assay using a tissue microarray procedure in pancreatic cancer tissues and cells with different degrees of differentiation. A loss-of-function approach was used to examine the effects of a lentivirus-mediated OCT4 small hairpin RNA vector on biological behaviors, including cell proliferative activity and invasive potential. The results demonstrated that the expression levels of OCT4 protein in cancer tissues were significantly elevated compared with those in adjacent non-cancerous tissues (65.0 vs. 42.5%; P=0.005), which was correlated with tumor differentiation (P=0.008). The knockdown of OCT4 inhibited the proliferation and invasion of pancreatic cancer cells (Panc-1) expressing high levels of OCT4, accompanied with decreased expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2). In conclusion, the present study reveals that the increased expression of OCT4 is correlated with the differentiation of pancreatic cancer, while knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of AKT pathway-mediated PCNA and MMP-2 expression, suggesting that OCT4 might serve as a potential therapeutic target for the treatment of pancreatic cancer.

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Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy

Cited by 19 publications

References 25 publications

Genome-Wide Microarray Expression and Genomic Alterations by Array-CGH Analysis in Neuroblastoma Stem-Like Cells

Genome-Wide Microarray Expression and Genomic Alterations by Array-CGH Analysis in Neuroblastoma Stem-Like Cells

Nonsyndromic cleft lip with or without cleft palate and cancer: Evaluation of a possible common genetic background through the analysis of GWAS data

Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway

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