Transcription Factors in Cancer Stem Cells of the Hematopoietic Lineage

2009 ◽  
pp. 75-83 ◽  
Author(s):  
Steffen Koschmieder ◽  
Daniel G Tenen
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Hematopoietic Lineage

scholarly journals The Relevance of Transcription Factors in Gastric and Colorectal Cancer Stem Cells Identification and Eradication

2020 ◽  
Vol 8 ◽  
Author(s):  
Diana Pádua ◽  
Paula Figueira ◽  
Inês Ribeiro ◽  
Raquel Almeida ◽  
Patrícia Mesquita
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Colorectal Cancer Stem Cells

scholarly journals A83 INTESTINAL EPITHELIAL CELL STEMNESS AND DIFFERENTIATION ARE REGULATED BY THE HIPPO PATHWAY EFFECTOR YAP1

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 97-98
Author(s):  
S Fallah ◽  
J Beaulieu
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Hippo Pathway ◽  
High Rate ◽  
Intestinal Cell ◽  
Intestinal Differentiation ◽  
Ht29 Cells ◽  
The Hippo Pathway

Abstract Background The high rate of cell turnover in the intestinal epithelium is supported by the LGR5+ crypt base columnar (CBC) stem cells, which are located at the lower part of the gland. Among of the various factors and signals like Wnt and Notch, YAP1 (yes associated protein) also plays an important role in stemness of CBC stem cells. YAP1 is the effector of the Hippo pathway. Hippo Pathway restricts the cells proliferation, tissues overgrowth and cancer formation through the phosphorylation and inactivation of the YAP1 protein. When active, YAP1 transfers into nucleus, forms the complex with TEADs transcription factors and promotes the transcription of genes involved in cell growth and proliferation. Aims In the present study, we investigated the role of the YAP1 in the colorectal cancer multipotent HT29 cell line, which contain cancer stem cells (CSC). Methods For approaching to this goal, YAP1 expression was knocked down using shRNAs in HT29 cells. Then stem cells and intestinal cell lineages (secretory goblet, Paneth and enteroendocrine and absorptive) markers expression was analyzed using qPCR and Western blot. Results The results showed the reduction of the expression of stem cells markers including LGR5 in YAP1 knockdown HT29 cells compare with control. Expression of the goblet cells markers (MUC2 and trefoil factor 3) and absorptive cells markers (sucrase-isomaltase and dipeptidylpeptidase IV) were significantly increased in YAP1 knockdown cells but Paneth (DEFA5 and lysozyme) and enteroendocrine (CHGA) were not detected. Finally, examination of the main transcription factors for intestinal differentiation revealed an increase in CDX2 expression. Conclusions These results suggest that YAP1 is involved in the maintenance of colorectal cancer stem cells while preventing intestinal differentiation in both secretory and absorptive lineages through the repression of CDX2. Funding Agencies CIHR

scholarly journals RUNX1 and RUNX2 transcription factors function in opposing roles to regulate breast cancer stem cells

2020 ◽  
Vol 235 (10) ◽  
pp. 7261-7272
Author(s):  
Andrew J. Fritz ◽  
Deli Hong ◽  
Joseph Boyd ◽  
Jason Kost ◽  
Kristiaan H. Finstaad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells

STEM-14. THE WRAD COMPLEX REPRESENTS A THERAPEUTIC TARGET FOR CANCER STEM CELLS IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi23-vi24
Author(s):  
Kelly Mitchell ◽  
Joseph Alvarado ◽  
Christopher Goins ◽  
Steven Martinez ◽  
Jonathan Macdonald ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Self Renewal ◽  
Stem Cell Maintenance ◽  
Cell Maintenance

Abstract Glioblastoma (GBM) progression and resistance to conventional therapies is driven in part by cells within the tumor with stem cell properties including quiescence, self-renewal and drug efflux potential. It is thought that eliminating these cancer stem cells (CSCs) is a key component to successful clinical management of GBM. However, currently, few known molecular mechanisms driving CSCs can be exploited for therapeutic development. Core transcription factors such as SOX2, OLIG2, OCT4 and NANOG maintain the CSC state in GBM. Our laboratory recently uncovered a self-renewal signaling axis involving RBBP5 that is necessary and sufficient for CSC maintenance through driving expression of these core stem cell maintenance transcription factors. RBBP5 is a component of the WRAD complex, which promotes Lys4 methylation of histone H3 to positively regulate transcription. We hypothesized that targeting RBBP5 could be a means to disrupt epigenetic programs that maintain CSCs in stemness transcriptional states. We found that genetic and pharmacologic inhibition of the WRAD complex reduced CSC growth, self-renewal and tumor initiation potential. WRAD inhibitors partially dissembled the WRAD complex and reduced H3K4 trimethylation both globally and at the promoters of key stem cell maintenance transcription factors. Using a CSC reporter system, we demonstrated that WRAD complex inhibition decreased growth of SOX2/OCT4 expressing CSCs in a concentration-dependent manner as quantified by live imaging. Overall, our studies assess the function of the WRAD complex and the effect of WRAD complex inhibitors in preclinical models and specifically on the stem cell state for the first time in GBM. Studying the functions of the WRAD complex in CSCs may improve understanding of GBM pathogenesis and elucidate how CSCs survive despite aggressive chemotherapy and radiation. Our ongoing studies aim to develop brain penetrant inhibitors targeting the WRAD complex as an anti-CSC strategy that could potentially synergize with standard of care treatments.

scholarly journals Tackling Cancer Stem Cells via Inhibition of EMT Transcription Factors

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Megan Mladinich ◽  
Diane Ruan ◽  
Chia-Hsin Chan
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Ample Evidence ◽  
Mesenchymal Transition ◽  
Secondary Tumors ◽  
Patient Prognosis

Cancer stem cell (CSC) has become recognized for its role in both tumorigenesis and poor patient prognosis in recent years. Traditional therapeutics are unable to effectively eliminate this group of cells from the bulk population of cancer cells, allowing CSCs to persist posttreatment and thus propagate into secondary tumors. The therapeutic potential of eliminating CSCs, to decrease tumor relapse, has created a demand for identifying mechanisms that directly target and eliminate cancer stem cells. Molecular profiling has shown that cancer cells and tumors that exhibit the CSC phenotype also express genes associated with the epithelial-to-mesenchymal transition (EMT) feature. Ample evidence has demonstrated that upregulation of master transcription factors (TFs) accounting for the EMT process such as Snail/Slug and Twist can reprogram cancer cells from differentiated to stem-like status. Despite being appealing therapeutic targets for tackling CSCs, pharmacological approaches that directly target EMT-TFs remain impossible. In this review, we will summarize recent advances in the regulation of Snail/Slug and Twist at transcriptional, translational, and posttranslational levels and discuss the clinical implication and application for EMT blockade as a promising strategy for CSC targeting.

scholarly journals Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors

Leukemia ◽  
2012 ◽  
Vol 26 (9) ◽  
pp. 2124-2134 ◽  
Author(s):  
A Ikegame ◽  
S Ozaki ◽  
D Tsuji ◽  
T Harada ◽  
S Fujii ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Small Molecule ◽  
Hla Class I ◽  
Class I ◽  
Antibody Targeting
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