Prognostic significance of NANOG and KLF4 for breast cancer

Department of Surgery and Science, Graduate School of Research Into Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, Japan, .
Breast Cancer (Impact Factor: 1.59). 04/2012; 21(1). DOI: 10.1007/s12282-012-0357-y
Source: PubMed


BACKGROUND: Some of the induced pluripotent stem cell (iPS cell)-inducing factors have been reported to be expressed in breast cancer. The aim of the present study was to examine the relationship between the expression of iPS cell-inducing factors and the prognosis of breast cancer patients. METHODS: In 100 breast cancer patients, the expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 was determined by immunohistochemistry using a tissue microarray analysis. RESULTS: Patients with strong expression of NANOG had significantly lower disease-free survival (DFS) and overall survival rates than those with weak expression of NANOG (P = 0.004 and 0.033, respectively). In contrast, patients with strong expression of KLF4 had better DFS (P = 0.014). CONCLUSIONS: Strong expression of NANOG is an indicator of a poor prognosis for breast cancer patients, whereas KLF4 is a favorable prognostic indicator. Our results suggest that NANOG stimulates the growth and metastasis of breast cancer cells, whereas KLF4 inhibits these processes.

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    • "It is the imbalance that determines the individual outcome (Figure 1). For example, NANOG expression is an indicator of poor prognosis stimulating the growth and metastasis of breast cancer cells, whereas KLF4 is a favorable prognostic indicator inhibiting these processes.55 2) The correlation between two factors is, at least in some cases, more significant than the overall expression of either. "
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    ABSTRACT: Breast cancer remains the leading cause of cancer-related mortality in women. Comprehensive genomics, proteomics, and metabolomics studies are emerging that offer an opportunity to model disease biology, prognosis, and response to specific therapies. Although many biomarkers have been identified through advances in data mining techniques, few have been applied broadly to make patient-specific decisions. Here, we review a selection of breast cancer prognostic indicators and their implications. Our goal is to provide clinicians with a general evaluation of emerging computational methodologies for outcome prediction.
    Cancer Management and Research 07/2014; 6(1):301-12. DOI:10.2147/CMAR.S46483
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    • "Nasopharyngeal cancer Clinical prognosis Wang et al. (2012) Melanoma Cell invasion Girouard et al. (2012) Colon cancer Cell invasion and metastases Neumann et al. (2011) Osteosarcomas Survival and self-renewal Basu-Roy et al. (2012) Gastric cancer Matsuoka et al. (2012) Lung cancer Transformation Chen et al. (2012) Prostate cancer Jia et al. (2011b) Breast cancer Stolzenburg et al. (2012) Oct4 Gastric cancer Negative prognostic factor Matsuoka et al. (2012) Oral squamous cell carcinoma Chiou et al. (2008) and Tsai et al. (2011) Klf4 Breast cancer Good prognosis Nagata et al. (2012) Leukemias Different Klf4 mRNA levels mirror differentiation state, not a prognostic factor Guo and Tang (2012) Squamous cell carcinoma Poor prognosis Chen et al. (2008) Breast cancer Rowland et al. (2005) Nanog Hepatocellular carcinoma Shan et al. (2012) Breast cancer Poor prognosis Nagata et al. (2012) Oral squamous cell carcinoma (OSCC) (Nanog/Oct-4/CD133 coexpression) Poor prognosis Chiou et al. (2008) Continued oncogenes such as c-Myc in epithelial tumors is sufficient to reactivate an ES cell-like transcriptional signature. Other reprogramming factors, such as Sox2 and Lin28, have been documented as oncogenes in small cell lung and esophageal squamous-cell carcinomas and germ-cell tumors (Bass et al., 2009; West et al., 2009). "
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    ABSTRACT: Rapid progress made in various areas of regenerative medicine in recent years occurred both at the cellular level, with the Nobel prize-winning discovery of reprogramming (generation of induced pluripotent stem (iPS) cells) and also at the biomaterial level. The use of four transcription factors, Oct3/4, Sox2, c-Myc, and Klf4 (called commonly "Yamanaka factors") for the conversion of differentiated cells, back to the pluripotent/embryonic stage, has opened virtually endless and ethically acceptable source of stem cells for medical use. Various types of stem cells are becoming increasingly popular as starting components for the development of replacement tissues, or artificial organs. Interestingly, many of the transcription factors, key to the maintenance of stemness phenotype in various cells, are also overexpressed in cancer (stem) cells, and some of them may find the use as prognostic factors. In this review, we describe various methods of iPS creation, followed by overview of factors known to interfere with the efficiency of reprogramming. Next, we discuss similarities between cancer stem cells and various stem cell types. Final paragraphs are dedicated to interaction of biomaterials with tissues, various adverse reactions generated as a result of such interactions, and measures available, that allow for mitigation of such negative effects.
    International review of cell and molecular biology 01/2014; 308:167-203. DOI:10.1016/B978-0-12-800097-7.00005-1 · 3.42 Impact Factor
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    • "MCF-10A normal mammary epithelium showed increased migration after knockdown of KLF4. In specimens of lung, gastric and prostate cancer, KLF4 also demonstrated decreased levels of expression when compared with normal tissue counterparts [37,88-92]. Restoration of KLF4 expression in vitro impaired migration and invasion of prostate cancer cells [37]. "
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    ABSTRACT: Krüppel-like factors (KLFs) comprise a highly conserved family of zinc finger transcription factors, that are involved in a plethora of cellular processes, ranging from proliferation and apoptosis to differentiation, migration and pluripotency. During the last few years, evidence on their role and deregulation in different human cancers has been emerging. This review will discuss current knowledge on Krüppel-like transcription in the epithelial-mesenchymal transition (EMT), invasion and metastasis, with a focus on epithelial cancer biology and the extensive interface with pluripotency. Furthermore, as KLFs are able to mediate different outcomes, important influences of the cellular and microenvironmental context will be highlighted. Finally, we attempt to integrate diverse findings on KLF functions in EMT and stem cell biology to fit in the current model of cellular plasticity as a tool for successful metastatic dissemination.
    Oncotarget 11/2013; 5(1). DOI:10.18632/oncotarget.1456 · 6.36 Impact Factor
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