Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA340149 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Wnt/β-catenin signaling is activated in colorectal cancer (CRC) and is involved in CRC growth. Tankyrase, a poly(ADP-ribose) polymerase family member, destabilizes Axin and positively regulates the Wnt/β-catenin signaling. Tankyrase inhibitors efficiently suppress CRC cell proliferation. We established 320-IWR cells, which showed resistance to tankyrase inhibitor IWR-1, from human CRC COLO-320DM cells. We analyzed gene expression profile of 320-IWR cells (320IWR_1,_2) and parental COLO-320DM cells (COLO320_1,_2).
2016-11-01 | GSE86061 | GEO
Project description:In colorectal cancer (CRC), WNT/β-catenin signaling is aberrantly activated mainly by loss-of-function mutations in adenomatous polyposis coli (APC) and is involved in tumor progression. Tankyrase inhibitors, which suppress WNT/β-catenin signaling, are under pre-clinical and clinical trials, while their resistance mechanisms remain unclear. In this study, we established tankyrase inhibitor-resistant CRC cells, JC73-RK100, from APC-mutated patient-derived CRC cells. JC73-RK100 cells and several CRC cells were sensitive to tankyrase inhibitors at low concentrations but were resistant at high concentrations (i.e., bell-shaped dose response: BSDR). Mechanistically, tankyrase inhibitors at high concentrations promoted BRD3/4-dependent E2F target gene transcription and over-activated cell cycle progression in the BSDR cells. BET inhibitors canceled the bell-shaped dose response to tankyrase inhibitors. Taken together, these observations suggest that combination of tankyrase and BET inhibitors would be a useful therapeutic approach to overcome a subset of resistance to tankyrase inhibitors.
2024-07-29 | GSE239681 | GEO
Project description:In colorectal cancer (CRC), WNT/β-catenin signaling is aberrantly activated mainly by loss-of-function mutations in adenomatous polyposis coli (APC) and is involved in tumor progression. Tankyrase inhibitors, which suppress WNT/β-catenin signaling, are under pre-clinical and clinical trials, while their resistance mechanisms remain unclear. In this study, we established tankyrase inhibitor-resistant CRC cells, JC73-RK100, from APC-mutated patient-derived CRC cells. JC73-RK100 cells and several CRC cells were sensitive to tankyrase inhibitors at low concentrations but were resistant at high concentrations (i.e., bell-shaped dose response: BSDR). Mechanistically, tankyrase inhibitors at high concentrations promoted BRD3/4-dependent E2F target gene transcription and over-activated cell cycle progression in the BSDR cells. BET inhibitors canceled the bell-shaped dose response to tankyrase inhibitors. Taken together, these observations suggest that combination of tankyrase and BET inhibitors would be a useful therapeutic approach to overcome a subset of resistance to tankyrase inhibitors.
2024-07-29 | GSE239680 | GEO
Project description:Strong activation of the oncogenic Wnt/beta-catenin pathway is a main mechanism of resistance to FOXO3a-induced apoptosis promoted by PI3K and AKT inhibitors in colorectal cancer (CRC). Reducing Wnt/beta-catenin activity would sensitize colorectal tumors to these inhibitors. However, no Wnt/beta-catenin signaling inhibitor has proven clinical potential yet. Recently, inhibitors that block tankyrases were shown to reduce colon cancer cell proliferation by decreasing nuclear beta-catenin. We aim to identify determinants of response to these novel Wnt-inhibitors. Therefore, we treated in vivo three different patient-derived xenograft models (PDX; P2, P5 and P30) growing subcutaneously in NOD SCID mice with the novel tankyrase inhibitor NVP-TNKS656.
2015-08-10 | E-MTAB-2446 | biostudies-arrayexpress
Project description:Tankyrase enhances beta-catenin signaling via PARsylation and subsequent degradation of Axin, a negative regulator of beta-catenin. Tankyrase inhibitors stabilize Axin and suppress beta-catenin signaling. We developed a novel tankyrase inhibitor, RK-287107. We used microarrays to elucidate the gene expression profile of human colorectal cancer cells treated with RK-287107 in a mouse xenograft model.
2018-12-26 | GSE113965 | GEO
Project description:Cancer-associated fibroblasts (CAFs) are an important component of the desmoplastic stroma in rectal cancer. Preoperative chemoradiotherapy plays a pivotal role in the management of locally advanced rectal cancer. Patient-derived CAFs were used to evaluate the response to radiotherapy and its consequent impact on colorectal cancer cells (COLO320DM). COLO320DM cells were seeded and 24 hours later 1.8Gy irradiated. Subsequently, 24h later COLO320DM cells were treated with the secretome of 10x 1.8Gy irradiated CAFs or sham treated CAFs in 0.5% of serum. RNA was isolated 6 hours or 48 hours later.
2017-11-01 | E-MTAB-5364 | biostudies-arrayexpress
Project description:Expression of BRAF inhibitor resistant colon cancer lines
| PRJNA149929 | ENA
Project description:First, in a model of xenografts induced with HT-29 human colon cancer cells, we demonstrated that the transcription factor NF-kB was involved in the resistance to CPT-11. Then, from one tumor treated with CPT-11 plus a NF-kB inhibitor, we established a resistant cell line to CPT-11. The aim of this study was to compare the expression of genes involved in the signaling pathway of NF-kB between the sensitive and the resistant cell lines and to identify other genes (target or not of NF-kB) which the expression was modified when the resistant phenotype was acquired. Human colon cancer cells chemosensitive (HT-29) versus human colon cancer cells chemoresistant (RIV) in a dye-swap experiment.
2012-08-23 | E-GEOD-23433 | biostudies-arrayexpress
Project description:Colon cancer cell lines with partial sensitivity to the BRAF inhibitor PLX4720 were grown in increasing concentration of the drug to develop acquired resistance. Gene expression was performed for comparison of the resistant clones to the parental lines. Colon cancer cell lines with partial sensitivity to the BRAF inhibitor PLX4720 were grown in increasing concentration of the drug to develop acquired resistance. Gene expression was performed for comparison of the resistant clones to the parental lines.
2012-09-15 | E-GEOD-34299 | biostudies-arrayexpress
Project description:Tankyrase, a poly(ADP-ribose) polymerase family member, destabilizes Axin and positively regulates the Wnt/β-catenin signaling. We demonstrated that tankyrase inhibitors can target the colorectal cancer stem-like cells. Tankyrase inhibitors efficiently suppress colorectal cancer stem-like cell proliferation via AXIN-dependent manner. We sorted CD44-positive COLO-320DM cells, which showed a characteristic of CSCs and were targeted by tankyrase inhibitors. We analyzed gene expression profile of CD44-positive cells (CD44-positive 01, 02, 03) and CD44-negative cells (CD44-negative 01, 02, 03).
2020-05-05 | GSE130750 | GEO