Prognostic significance of NANOG and KLF4 for breast cancer.
ABSTRACT 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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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 01/2014; 6:301-12.
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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. · 4.97 Impact Factor
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ABSTRACT: Involvement of cancer stem cells (CSC) in initiation, progression, relapse, and therapy-resistance of colorectal cancer (CRC) warrants search for small molecules as 'adjunct-therapy' to target both colon CSC and bulk tumor population. Herein, we assessed the potential of silibinin to eradicate colon CSC together with associated molecular mechanisms. In studies examining how silibinin modulates dynamics of CSC spheroids in terms of its effect on kinetics of CSC spheroids generated in presence of mitogenic and interleukin (IL)-mediated signaling which provides an autocrine/paracrine amplification loop in CRC, silibinin strongly decreased colon CSC pool together with cell survival of bulk tumor cells. Silibinin effect on colon CSC was mediated via blocking of pro-tumorigenic signaling, notably IL-4/-6 signaling that affects CSC population. These silibinin effects were associated with decreased mRNA and protein levels of various CSC-associated transcription factors, signaling molecules and markers. Furthermore, 2D and 3D differentiation assays indicated formation of more differentiated clones by silibinin. These results highlight silibinin potential to interfere with kinetics of CSC pool by shifting CSC cell division to asymmetric type via targeting various signals associated with the survival and multiplication of colon CSC pool. Together, our findings further support clinical usefulness of silibinin in CRC intervention and therapy.Oncotarget 06/2014; · 6.64 Impact Factor