Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA118493 | ENA |
REPOSITORIES: ENA
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Project description:Wnt signalling maintains the undifferentiated state of intestinal crypt/progenitor cells through the TCF4/Ã-catenin activating transcriptional complex. In colorectal cancer, activating mutations in Wnt pathway components lead to inappropriate activation of the TCF4/Ã-catenin transcriptional program and tumourigenesis in the gut epithelium. The mechanisms by which TCF4/Ã-catenin activate key target genes are not well understood. Using a proteomics approach, we identified Tnik, a member of the Germinal centre kinase family, as a Tcf4 interactor in the proliferative crypts of mouse small intestine. Tnik is recruited to promoters of Wnt target genes in mouse crypts and in Ls174T colorectal cancer cells in a Ã-catenin dependent manner. Depletion of TNIK and expression of TNIK kinase mutants abrogated TCF-LEF transcription, highlighting the essential role of the kinase activity in Wnt target gene activation. siRNA depletion of TNIK followed by expression array analysis demonstrated that TNIK is an essential and exclusive activator of Wnt induced transcriptional program. As an essential component in the TCF4/Ã-catenin activator complex, the kinase TNIK may present an attractive candidate for drug targeting in colorectal cancer. HEK293T cells: Wnt3A vs control medium (CM) induction for 4, 7 and 9 hours; si-TNIK vs si-control after Wnt3A induction at 4 and 7 hours (2 biological replicates for 7 hour time point); dyeswap for each experiment (i.e. 12 arrays in total).
2010-08-18 | E-GEOD-17623 | biostudies-arrayexpress
Project description:Wnt signalling maintains the undifferentiated state of intestinal crypt/progenitor cells through the TCF4/ß-catenin activating transcriptional complex. In colorectal cancer, activating mutations in Wnt pathway components lead to inappropriate activation of the TCF4/ß-catenin transcriptional program and tumourigenesis in the gut epithelium. The mechanisms by which TCF4/ß-catenin activate key target genes are not well understood. Using a proteomics approach, we identified Tnik, a member of the Germinal centre kinase family, as a Tcf4 interactor in the proliferative crypts of mouse small intestine. Tnik is recruited to promoters of Wnt target genes in mouse crypts and in Ls174T colorectal cancer cells in a ß-catenin dependent manner. Depletion of TNIK and expression of TNIK kinase mutants abrogated TCF-LEF transcription, highlighting the essential role of the kinase activity in Wnt target gene activation. siRNA depletion of TNIK followed by expression array analysis demonstrated that TNIK is an essential and exclusive activator of Wnt induced transcriptional program. As an essential component in the TCF4/ß-catenin activator complex, the kinase TNIK may present an attractive candidate for drug targeting in colorectal cancer.
2009-08-13 | GSE17623 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Background: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Methods: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified eleven candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Results: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. Conclusion: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients.
2016-07-22 | GSE71222 | GEO
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:Background: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Methods: The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified eleven candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients. Results: Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients. Conclusion: This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients. Gene expression profiles for 152 cancer tissues from colorectal cancer patients were measured by Affymetrix HG-U133 Plus 2.0 arrays. Normalization was performed by robust multi-array average (RMA) method under R 2.12.1 statistical software with affy package from BioConductor. The normalized gene expression levels were presented as log2-transformed values by RMA.
2016-07-22 | E-GEOD-71222 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4686780 | biostudies-literature
Project description:Introduction: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Experimental design: The expression profiles of cancer cells in 153 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 271 CRC patients. Results: Using microarray analysis, we identified 11 candidate genes related to distant metastases in CRC patients. Among these genes, Traf2- and Nck- interacting kinase (TNIK) was known to be associated with aggressiveness in CRC through Wnt signaling. Absence of overexpression of TNIK protein was associated with significantly better overall survival (p < 0.001) and relapse-free survival (p < 0.001). Moreover, overexpression of TNIK protein was an independent risk factor for CRC recurrence (p = 0.009). Conclusion: Overexpression of TNIK might be a predictive biomarker of CRC recurrence.
2015-11-21 | GSE64257 | GEO
Project description:Introduction: The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC). Experimental design: The expression profiles of cancer cells in 153 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells, especially in patients with distant metastases, was a prerequisite to select candidate genes. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study and investigated the relationship between protein expression and clinicopathologic features in 271 CRC patients. Results: Using microarray analysis, we identified 11 candidate genes related to distant metastases in CRC patients. Among these genes, Traf2- and Nck- interacting kinase (TNIK) was known to be associated with aggressiveness in CRC through Wnt signaling. Absence of overexpression of TNIK protein was associated with significantly better overall survival (p < 0.001) and relapse-free survival (p < 0.001). Moreover, overexpression of TNIK protein was an independent risk factor for CRC recurrence (p = 0.009). Conclusion: Overexpression of TNIK might be a predictive biomarker of CRC recurrence.
2015-11-21 | GSE64256 | GEO
Project description: Not available
| S-EPMC3743458 | biostudies-literature