Project description:Dysregulation of Wnt/TCF signaling is closely associated with cancers arising from the gastrointestinal tract, inlcluding colon cancer and liver cancer. The goal of this study is to understand the transcriptional programs underlying Wnt/TCF activation in gastrointestinal cancers. We examined the transcriptional responses to TCF inhibition in cultured human colon cancer cells and liver cancer cells that are characteristic of Wnt pathway activation. Human liver cancer cell line HepG2 and colon cancer cell line LS174T with or without expression of a dominant negative form of TCF4
Project description:Dysregulation of Wnt/TCF signaling is closely associated with cancers arising from the gastrointestinal tract, inlcluding colon cancer and liver cancer. The goal of this study is to understand the transcriptional programs underlying Wnt/TCF activation in gastrointestinal cancers. We examined the transcriptional responses to TCF inhibition in cultured human colon cancer cells and liver cancer cells that are characteristic of Wnt pathway activation.
Project description:FoxA transcription factors are involved in development and tumorigenesis of the gastrointestinal tract. However, the downstream programs controlled by FoxA factors remain poorly understood. The goal of this study is to understand the transcriptional responses regulated by FoxA proteins in liver and colon cancer cells. Human liver cancer cell line HepG2 and colon cancer cell line LS174T infected with lentivirus expressing shRNAs targeting human FoxA1 and FoxA2.
Project description:The effect of ER-stress and subsequent activation of the unfolded protein response was investigated in colon cancer stem cells and more differentiated colon cancer cells Human colon cancer derived spheroid cultures with a TCF/LEF driven GFP reporter for Wnt signaling activity were treated for 24 hours with SubAB or protease-dead SubABco (1µg/ml) Treated spheroid cultures were sorted into colon-cancer stem cell fraction (highest 10% Wnt-GFP) and differentiated colon cancer fraction (10% Lowest(Wnt Low) for micro array
Project description:Hypnea musciformis is a red macroalga that is widely distributed in tropical and subtropical regions. It is known to contain various bioactive compounds, including sulfated polysaccharides, flavonoids, and phlorotannins. Recent studies have investigated the potential anticancer effects of extracts from Hypnea musciformis demonstrating their have cytotoxic effects on various cancer cell lines. The anticancer effects of these extracts are thought to be due to the presence of bioactive compounds, which have been shown to have antitumor and immunomodulatory effects. However, further studies are needed to fully understand the molecular mechanisms that underlie these anticancer effects and to determine their potential as therapeutic agents for cancer treatment. We have performed transcriptome and proteome analysis in liver and colon cancer human cell lines following treatment with Hypnea musciformis macroalgae extracts to characterize its anti-tumor effect in detail at the molecular level and to link transcriptome and proteome responses to the observed phenotypes in vitro. We have identified that treatment with the macroalgae extract triggers p53-mediated response at the transcriptional and protein level in liver cancer cells, in contrast to colon cancer cells in which the effects are associated with metabolic changes. Overall, the available evidence suggests that extracts from Hypnea musciformis have the potential to serve as a source of anticancer agents in liver cancer cells through the activation of a p53-mediated anti-tumor response that is linked to inhibition of cellular proliferation and induction of apoptosis.
Project description:The WNT-TCF signaling pathway participates in adult tissue homeostasis and repair, and is hyperactive in a number of human diseases including cancers of the colon. Whereas to date there are no antagonists approved for patient use, a potential problem for their sustained use is the blockade of WNT signaling in healthy tissues, thus provoking potentially serious co-lateral damage. Here we have screened a library of plant and microorganism small molecules for novel WNT signaling antagonists and describe withanolide F as a potent WNT-TCF response blocker. This steroidal lactone inhibits TCF-dependent colon cancer xenograft growth and mimics the effects of genetic blockade of TCF and of ivermectin, a previously reported WNT-TCF blocker. However, withanolide F is unique in that it imposes a long-lasting repression of tumor growth, WNT-TCF targets and cancer stem cell clonogenicity long after drug treatment
Project description:Deregulation of canonical Wnt/beta-catenin pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 (beta-catenin gene) are highly frequent in colon cancer and cause aberrant stabilization of b-catenin, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of b-catenin by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of beta-catenin in colon cancer cells (GSE53656). Immunoprecipitated samples from human colon cancer SW480 cells with antibodies against beta-catenin and control IgG respectively were used for ChIP-seq experiments.