Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA339109 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation profiling of four DLD1 colorectal cancer cell derivatives that recapitulate EMT/MET transitions during metastasis. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs. Overall design: Bisulphite converted DNA from four DLD1 colorectal cancer cell line derivatives were analyzed with the Illumina Infinium 450k Human Methylation Beadchip
2017-03-28 | GSE85529 | GEO
Project description:microRNA profiling of a cellular model of colorectal cancer progression, which is based on four defined derivates of a CRC cell line that resulted from EMT/MET transitions and phenotypically recapitulate the metastatic cascade: epithelial-like primary tumor, mesenchymal-like tumor cells growing in soft agar or as colonospheres, and mouse xenografts of the latter resulting in lung-metastasis comprised of epithelial-state cells. Overall design: Colorectal cancer cell line DLD1 and its derivatives were maintained in McCoy`s 5A Medium (Invitrogen) containing 10% fetal bovine serum (FBS, Invitrogen), 100 units/ml penicillin and 0.1 mg/ml streptomycin.
2017-03-28 | GSE85687 | GEO
Project description:RNA profiling of a cellular model of colorectal cancer progression, which is based on four defined derivates of a CRC cell line that resulted from EMT/MET transitions and phenotypically recapitulate the metastatic cascade: epithelial-like primary tumor, mesenchymal-like tumor cells growing in soft agar or as colonospheres, and mouse xenografts of the latter resulting in lung-metastasis comprised of epithelial-state cells. Overall design: Colorectal cancer cell line DLD1 and its derivatives were maintained in McCoy`s 5A Medium (Invitrogen) containing 10% fetal bovine serum (FBS, Invitrogen), 100 units/ml penicillin and 0.1 mg/ml streptomycin.
2017-03-28 | GSE85685 | GEO
Project description:RNA profiling of four DLD1 colorectal cancer cell derivatives that recapitulate EMT/MET transitions during metastasis.
| PRJNA339111 | ENA
Project description:DNA methylation profiling of four DLD1 colorectal cancer cell derivatives that recapitulate EMT/MET transitions during metastasis.
| PRJNA338751 | ENA
Project description:H3K4me3, H3K27me3, and H3K79me3 profiling of a cellular model of colorectal cancer progression, which is based on four defined derivates of a CRC cell line that resulted from EMT/MET transitions and phenotypically recapitulate the metastatic cascade: epithelial-like primary tumor, mesenchymal-like tumor cells growing in soft agar or as colonospheres, and mouse xenografts of the latter resulting in lung-metastasis comprised of epithelial-state cells. Overall design: H3K4me3, H3K27me3, and H3K79me3
2017-03-28 | GSE85766 | GEO
Project description:INTRODUCTION:C-Met plays important roles in treatment resistance, tumor invasion, and metastasis. In this study, we used a small molecule inhibitor of c-Met, crizotinib, in cetuximab-resistant, mutant KRAS-driven colorectal cancer cell lines and assessed radiosensitization. MATERIALS AND METHODS:A tissue microarray containing colorectal tumors was used to study the relationship between KRAS mutations and c-Met expression. For in vivo studies, we used the KRAS mutant cell lines HCT116, DLD1, and LoVo. Colony formation assays were performed to assess the effects of crizotinib and cetuximab. Immunoblot analysis was used to determine the effect of crizotinib on c-Met and downstream pathways and DNA damage response. We then selected noncytotoxic doses of crizotinib to assess clonogenic survival with radiation. To study potential mechanisms of radiosensitization, cell cycle analysis was performed using flow cytometry. RESULTS:Analysis of the tissue microarray revealed that KRAS mutant tumors had active c-Met signaling. KRAS mutant cell lines LoVo, HCT116, and DLD1 were resistant to cetuximab but sensitive to crizotinib. Pretreatment with crizotinib for 24?hours radiosensitized LoVo, DLD1, and HCT116 cell lines with enhancement ratios of 1.54, 1.23, and 1.30, respectively. Immunoblot analysis showed that crizotinib blocked radiation-induced c-Met phosphorylation and attenuated downstream signaling pathways. Cell cycle analysis revealed minimal G1 arrest with crizotinib. Additionally, crizotinib completely blocked HGF induced cell migration. CONCLUSIONS:Inhibition of c-Met with crizotinib effectively sensitizes cetuximab-resistant KRAS mutant colorectal cancer cell lines to radiation. Crizotinib has the potential to improve outcomes in locally advanced rectal cancer patients undergoing chemoradiation.
2019-01-01 | S-EPMC6226619 | BioStudies
Project description:Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells. Using a miR-145 luciferase reporter assay, we determined that ectopic SNAI1 expression significantly repressed the miR-145 promoter. DLD1-SNAI1 and HCT116-SNAI1 cells demonstrated decreased RT sensitivity and, conversely, miR-145 replacement significantly enhanced RT sensitivity. Of the five parental colon cancer cell lines, SW620 cells demonstrated relatively high endogenous SNAI1 and low miR-145 levels. In the SW620 cells, miR-145 replacement decreased CSC-related transcription factor expression, spheroid formation, and radiation resistance. In rectal cancer patient-derived xenografts, CSC identified by EpCAM+/aldehyde dehydrogenase (ALDH)+ demonstrated high expression of SNAI1, c-Myc, and Nanog compared with non-CSCs (EpCAM+/ALDH-). Conversely, patient-derived CSCs demonstrated low miR-145 expression levels relative to non-CSCs. These results suggest that the SNAI1:miR-145 pathway represents a novel therapeutic target in colorectal cancer to overcome RT resistance.
2018-01-01 | S-EPMC5910672 | BioStudies
Project description:Epithelial-to-mesenchymal transition (EMT) has been associated with poor treatment outcomes in various malignancies and is inversely associated with miRNA145 expression. Therefore, we hypothesized that SNAI2 (Slug) may mediate 5-fluorouracil (5FU) chemotherapy resistance through inhibition of miR145 in colorectal cancer and thus represents a novel therapeutic target to enhance current colorectal cancer treatment strategies. Compared with parental DLD1 colon cancer cells, 5FU-resistant (5FUr) DLD1 cells demonstrated features of EMT, including >2-fold enhanced invasion (P < 0.001) and migration, suppressed E-cadherin expression, and 2-fold increased SNAI2 expression. DLD1 and HCT116 cells with stable expression of SNAI2 (DLD1/SNAI2; HCT116/SNAI2) also demonstrated EMT features such as the decreased E-cadherin as well as significantly decreased miR145 expression, as compared with control empty vector cells. On the basis of an miR145 luciferase promoter assay, we demonstrated that SNAI2 repressed activity of the miR145 promoter in the DLD1 and HCT116 cells. In addition, the ectopic expressing SNAI2 cell lines demonstrated decreased 5FU sensitivity, and, conversely, miR145 replacement significantly enhanced 5FU sensitivity. In the parental SW620 colon cancer cell line with high SNAI2 and low miR145 levels, inhibition of SNAI2 directly with short hairpin sequence for SNAI2 and miR145 replacement therapy both decreased vimentin expression and increased in vitro 5FU sensitivity. In pretreatment rectal cancer patient biopsy samples, low miR145 expression levels correlated with poor response to neoadjuvant 5FU-based chemoradiation. These results suggested that the SNAI2:miR145 pathway may represent a novel clinical therapeutic target in colorectal cancer and may serve as a response predictor to chemoradiation therapy.
2014-01-01 | S-EPMC4221636 | BioStudies
Project description:Distant metastasis is the primary cause of cancer-related death among patients with colorectal cancer (CRC), and the discovery of novel therapeutic targets by further exploring the molecular mechanisms of CRC metastasis is therefore urgently needed. We previously illustrated that CDC27 overexpression promoted proliferation in CRC, but no studies have emphasized the role of CDC27 in cancer metastasis thus far. Our previous data indicated that the expression of CDC27 was significantly associated with distant metastasis in patient tissues, and therefore, in this study, we focused on the investigation of the potential mechanisms of CDC27 in CRC metastasis. The results revealed that CDC27 promoted the metastasis, invasion and sphere-formation capacity of DLD1 cells, but that the inhibition of CDC27 in HCT116 cells suppressed metastasis both in vitro and in vivo. Mechanistic analyses revealed that CDC27 promoted epithelial-to-mesenchymal transition (EMT), as demonstrated by the reduced expression of the epithelial markers ZO-1 and E-cadherin and the enhanced expression of the mesenchymal markers ZEB1 and Snail in HCT116 and DLD1 cells. Further mechanistic investigation indicated that CDC27 promoted metastasis and sphere-formation capacity in an ID1-dependent manner. In conclusion, we first demonstrated the role of CDC27 in cancer metastasis and showed that CDC27 may serve as a promising therapeutic target for CRC.
1000-01-01 | S-EPMC5595092 | BioStudies