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Homo sapiens

ABSTRACT: Treatment of SW480 colon cancer cell induced xenografts with AZD and DBZ

PROVIDER: PRJNA386891 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5560390.fastq.gz	Fastqsanger.gz
	SRR5560391.fastq.gz	Fastqsanger.gz
	SRR5560392.fastq.gz	Fastqsanger.gz
	SRR5560393.fastq.gz	Fastqsanger.gz
	SRR5560394.fastq.gz	Fastqsanger.gz

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ERbeta modulation of NFkB pathway in colon cancer cell lines SW480 and HT29

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Project description:The WWOX gene is a tumor suppressor probably involved in regulation of cell cycle and apoptosis and downregulated in variety of cancer types.However, its role in colon cancerogenesis is unknown. The aim of this study was to characterize how WWOX may be involved in colon cancerogenesis or cancer progression, how it influences the basic cancer cell features and modifies cell expression profile.Our observations suggest that in HT29 colon cancer cell line increased expression of WWOX may result in transition of cancer cells into more normal- like colon epithelium phenotype, on the other hand in SW480 WWOX revealed the well-known tumour suppressor properties. However, as the colon cancer is very heterogeneous disease, obtained discrepancies may reflect the known differences between cell lines and cancerogenesis pathway, which they undergone. SW480 colon cancer cells were stably transfected with WWOX cDNA. SW480 cells transfected with an empty vector served as a control. Total mRNA was isolated to look for gene-expression differences induced by the WWOX overexpression.

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Treatment of SW480 colon cancer cell induced xenografts with AZD and DBZ

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Project description:Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide a unique tool to address these questions but studies are scarce. We report a differentiation system toward enterocytes and goblet cells, the two major colonic epithelial cell lineages, using organoids from human healthy tissue. Culture of normal patient-derived colon organoids in medium lacking stemness agents resulted in a modest ultrastructural differentiation phenotype with low-level expression of enterocyte (KLF4, KRT20, CA1) and goblet cell (TFF2, TFF3, AGR2) lineage markers. BMP pathway activation through depletion of Noggin and addition of BMP4 resulted in enterocyte-biased differentiation. Contrarily, blockade of the Notch pathway using the g-secretase inhibitor dibenzazepine (DBZ) favored goblet cell differentiation. Combination treatment with BMP4 and DBZ caused a balanced strong induction of both lineages. In contrast, colon tumor organoids responded poorly to BMP4 and DBZ showing only weak signals of cell differentiation. We also investigated the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on differentiation. Calcitriol attenuated the effects of the BMP4 and DBZ on normal colon organoids, with reduced expression of differentiation genes and phenotype. Consistently, in normal organoids, calcitriol inhibited early signaling by BMP4 as assessed by reduction of the level of phospho-SMAD1/5/8. Our results show that BMP and Notch signaling play key roles in human colon stem cell differentiation to the enterocytic and goblet cell lineages and that calcitriol modulates these processes favoring stemness features.

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