Abstract 5729: The Wnt transcription factor TCF4 mediates resistance of colorectal cancer cells to (chemo-) radiotherapy in a β-catenin-independent manner

2012 ◽  
Author(s):  
Marian Grade ◽  
Christine Eimer ◽  
Georg Emons ◽  
Emil Kendziorra ◽  
Melanie Spitzner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Independent Manner ◽  
Colorectal Cancer Cells

scholarly journals Zerumbone increases oxidative stress in a thiol‐dependent ROS ‐independent manner to increase DNA damage and sensitize colorectal cancer cells to radiation

2014 ◽  
Vol 4 (2) ◽  
pp. 278-292 ◽  
Author(s):  
Amit Deorukhkar ◽  
Niharika Ahuja ◽  
Armando‐Lopez Mercado ◽  
Parmeswaran Diagaradjane ◽  
Uma Raju ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Independent Manner ◽  
Colorectal Cancer Cells

scholarly journals SPIB Acts as a Tumor Suppressor by Activating NFkB and JNK Signaling Pathways Through MAP4K1 in Colorectal Cancer Cells

2020 ◽  
Author(s):  
Xunping Zhao ◽  
Lin Li ◽  
Shiyun Yuan ◽  
Qia Zhang ◽  
Xianyao Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Western Blot ◽  
Cancer Cells ◽  
Biological Function ◽  
Control Group ◽  
Inhibition Assay ◽  
Growth Inhibition Assay ◽  
Jnk Signaling ◽  
Colorectal Cancer Cells

Abstract BackgroundColorectal cancer (CRC) is one of the major cancers in the world. Spi-B Transcription Factor (SPIB) is one member of the E-twenty-six (ETS) transcription factor family. Previous studies have shown that the expression of SPIB is down-regulated in human colorectal cancer tissues. However, its biological function in colorectal cancer cells is not reported. The purpose of our study is to explore the biological function and related mechanism of SPIB in colorectal cancer cells, to provide reference for the molecular detection and targeted drug therapy of colorectal cancer.MethodsThe biological function of SPIB in colorectal cancer cells were studied by colony formation assay, CCK-8 cell proliferation assay, transwell assay, tube formation assay, flow cytometry analysis. Growth inhibition assay was used to measure the impact of SPIB on oxaliplatin and 5-fluorouracil (5-FU). Double luciferase reporter assay and western blot were used to detect mechanism of SPIB in colorectal cancer cells. ResultsSPIB mRNA was down-regulated in CRC cell lines and CRC tissues. SPIB can inhibit the proliferation, migration and invasion of CRC cells; can inhibit angiogenesis; and induce the cell cycle of CRC cells arrest in G2/M phase and promote the apoptosis of CRC cells. In the growth inhibition assay we found that compared with the control group, the 50% inhibitory concentration(IC50) values of oxaliplatin and 5-FU in the SPIB overexpression group were significantly reduced. Western blot results showed that the overexpression of SPIB up-regulated cleaved-PARP(c-PARP), nuclear factor kB p65 (NFkB p65), phospho-NFkB p65(p-NFkB P65), JNK1, and C-Jun proteins expression level compared with the control group. Double luciferase report experiment showed that SPIB can activate the promoter of MAP4K1 and enhance the expression of MAP4K1. After silencing MAP4K1, the protein expressions of c-PARP, NFkB P65, p-NFkB P65, JNK1, and C-Jun were down-regulated. ConclusionsIn this study, we found that SPIB is a tumor suppressor in colorectal cancer cells, SPIB sensitizes colorectal cancer cells to oxaliplatin and 5-FU. we also found that MAP4K1 is a target gene of SPIB, SPIB exerts its anti-colorectal cancer effect by activating NFkB and JNK signaling pathways through MAP4K1. The above findings may provide reference for new molecular markers and therapeutic targets for CRC.

scholarly journals TBX3 acts as tissue-specific component of the Wnt/β-catenin transcriptional complex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Dario Zimmerli ◽  
Costanza Borrelli ◽  
Amaia Jauregi-Miguel ◽  
Simon Söderholm ◽  
Salome Brütsch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Genes ◽  
Regulatory Elements ◽  
Dependent Manner ◽  
Independent Manner ◽  
Tissue Specific ◽  
Colorectal Cancer Cells ◽  
Transcriptional Complex

BCL9 and PYGO are β-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signaling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in developing mouse forelimbs, BCL9 proteins sustain the action of β-catenin in a largely PYGO-independent manner. Our genetic analyses implied that BCL9 necessitates other interaction partners in mediating its transcriptional output. We identified the transcription factor TBX3 as a candidate tissue-specific member of the β-catenin transcriptional complex. In developing forelimbs, both TBX3 and BCL9 occupy a large number of Wnt-responsive regulatory elements, genome-wide. Moreover, mutations in Bcl9 affect the expression of TBX3 targets in vivo, and modulation of TBX3 abundance impacts on Wnt target genes transcription in a β-catenin- and TCF/LEF-dependent manner. Finally, TBX3 overexpression exacerbates the metastatic potential of Wnt-dependent human colorectal cancer cells. Our work implicates TBX3 as context-dependent component of the Wnt/β-catenin-dependent transcriptional complex.

scholarly journals Quantitative Proteomics Identifies DNA Repair as a Novel Biological Function for Hepatocyte Nuclear Factor 4α in Colorectal Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 626 ◽  
Author(s):  
Jean-Philippe Babeu ◽  
Samuel D. Wilson ◽  
Élie Lambert ◽  
Dominique Lévesque ◽  
François-Michel Boisvert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Quantitative Proteomics ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Colorectal Cancer Cells ◽  
Hepatocyte Nuclear Factor 4Α

Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor that acts as a master regulator of genes for several endoderm-derived tissues, including the intestine, in which it plays a central role during development and tumorigenesis. To better define the mechanisms by which HNF4α can influence these processes, we identified proteins interacting with HNF4α using stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomics with either immunoprecipitation of green fluorescent protein (GFP) or with proximity-dependent purification by the biotin ligase BirA (BioID), both fused to HNF4α. Surprisingly, these analyses identified a significant enrichment of proteins characterized with a role in DNA repair, a so far unidentified biological feature of this transcription factor. Several of these proteins including PARP1, RAD50, and DNA-PKcs were confirmed to interact with HNF4α in colorectal cancer cell lines. Following DNA damage, HNF4α was able to increase cell viability in colorectal cancer cells. Overall, these observations identify a potential role for this transcription factor during the DNA damage response.

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