T1750 In Vitro and In Vivo Evidence in Support of Differentiation of Colon Cancer Stem Cells Into Adipocyte-Like Cells

2010 ◽  
Vol 138 (5) ◽  
pp. S-570
Author(s):  
Victor Nekrasov ◽  
Igor Titushkin ◽  
Michael Cho ◽  
Sarah C. Glover
Author(s):  
Lavanya Reddivari ◽  
Venkata Charepalli ◽  
Sridhar Radhakrishnan ◽  
Ramakrishna Vadde ◽  
Ryan J. Elias ◽  
...  

2012 ◽  
Vol 322 (1) ◽  
pp. 92-97 ◽  
Author(s):  
Xiao-ling Yin ◽  
Ning Wang ◽  
Xing Wei ◽  
Gan-feng Xie ◽  
Jian-jun Li ◽  
...  

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Anthony Essex ◽  
Javier Pineda ◽  
Grishma Acharya ◽  
Hong Xin ◽  
James Evans ◽  
...  

As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Evans et al., 2015), that described how we intended to replicate selected experiments from the paper ‘Wnt activity defines colon cancer stem cells and is regulated by the microenvironment’ (Vermeulen et al., 2010). Here, we report the results. Using three independent primary spheroidal colon cancer cultures that expressed a Wnt reporter construct we observed high Wnt activity was associated with the cell surface markers CD133, CD166, and CD29, but not CD24 and CD44, while the original study found all five markers were correlated with high Wnt activity (Figure 2F; Vermeulen et al., 2010). Clonogenicity was highest in cells with high Wnt activity and clonogenic potential of cells with low Wnt activity were increased by myofibroblast-secreted factors, including HGF. While the effects were in the same direction as the original study (Figure 6D; Vermeulen et al., 2010) whether statistical significance was reached among the different conditions varied. When tested in vivo, we did not find a difference in tumorigenicity between high and low Wnt activity, while the original study found cells with high Wnt activity were more effective in inducing tumors (Figure 7E; Vermeulen et al., 2010). Tumorigenicity, however, was increased with myofibroblast-secreted factors, which was in the same direction as the original study (Figure 7E; Vermeulen et al., 2010), but not statistically significant. Finally, we report meta-analyses for each results where possible.


2020 ◽  
Author(s):  
Anup Kumar Singh ◽  
Ayushi Verma ◽  
Akhilesh Singh ◽  
Rakesh Kumar Arya ◽  
Shrankhla Maheshwari ◽  
...  

AbstractDrug resistance is one of the trademark features of Cancer Stem Cells (CSCs). We and others have recently shown that paucity of functional death receptors (DR4/5) on the cell surface of tumor cells is one of the major reasons for drug resistance, but their involvement in the context of in CSCs is poorly understood. By harnessing CSC specific cytotoxic function of salinomycin, we discovered a critical role of epigenetic modulator EZH2 in regulating the expression of DRs in colon CSCs. Our unbiased proteome profiler array approach followed by ChIP analysis of salinomycin treated cells indicated that the expression of DRs, especially DR4 is epigenetically repressed in colon CSCs. Concurrently, EZH2 knockdown demonstrated increased expression of DR4/DR5, significant reduction of CSC phenotype such as spheroid formation in-vitro and tumorigenic potential in-vivo in colon cancer. TCGA data analysis of human colon cancer clinical samples shows strong inverse correlation between EZH2 and DR4. Taken together, this study provides an insight about epigenetic regulation of DR4 in colon CSCs and advocates that drug resistant colon cancer can be therapeutically targeted by combining TRAIL and small molecule EZH2 inhibitors.


2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Yoo‐Sun Kim ◽  
Sang‐Woon Choi ◽  
Soo Jin Min ◽  
Jisoo Lee ◽  
Yuri Kim

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
James Evans ◽  
Anthony Essex ◽  
Hong Xin ◽  
Nurith Amitai ◽  
Lindsey Brinton ◽  
...  

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by replicating selected results from a substantial number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (<xref ref-type="bibr" rid="bib5">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘Wnt activity defines colon cancer stem cells and is regulated by the microenvironment’ by Vermeulen and colleagues, published in Nature Cell Biology in 2010 (<xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>). The key experiments that will be replicated are those reported in Figures 2F, 6D, and 7E. In these experiments, Vermeulen and colleagues utilize a reporter for Wnt activity and show that colon cancer cells with high levels of Wnt activity also express cancer stem cell markers (Figure 2F; <xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>). Additionally, treatment either with conditioned medium derived from myofibroblasts or with hepatocyte growth factor restored clonogenic potential in low Wnt activity colon cancer cells in vitro (Figure 6D; <xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>) and in vivo (Figure 7E; <xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.


2016 ◽  
Author(s):  
Lavanya Reddivari ◽  
Venkata Charepalli ◽  
Ramakrishna Vadde ◽  
Sridhar Radhakrishnan ◽  
Joshua D. Lambert ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ramakrishna Vadde ◽  
Sridhar Radhakrishnan ◽  
Lavanya Reddivari ◽  
Jairam K. P. Vanamala

Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs) have the ability to drive continued expansion of the population of malignant cells. Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs). The total phenolic content, antioxidant activity, and phytochemical composition (LC-MS-MS) of methanol extract of triphala (MET) were also measured. We observed that MET contains a variety of phenolics including naringin, quercetin, homoorientin, and isorhamnetin. MET suppressed proliferation independent of p53 status in HCT116 and in HCCSCs. MET also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, MET inhibited HCCSCs colony formation, a measure of CSCs self-renewal ability. Anticancer effects of triphala observed in our study warrant future studies to determine its efficacyin vivo.


2016 ◽  
Vol 11 (5) ◽  
pp. 427-433 ◽  
Author(s):  
Lisette Potze ◽  
Simone di Franco ◽  
Jan H. Kessler ◽  
Giorgio Stassi ◽  
Jan Paul Medema

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