Whole Transcriptome Analysis Identifies TNS4 as a Key Effector of Cetuximab and a Regulator of the Oncogenic Activity of KRAS Mutant Colorectal Cancer Cell Lines
Abstract
:1. Introduction
2. Materials and Methods
2.1. Generation of Tumor Xenograft Mouse
2.2. RNA-seq Analysis
2.3. Cancer Cell Line Encyclopedia (CCLE) Data Analysis
2.4. The Cancer Genome Atlas (TCGA) Data Analysis
2.5. Gene Set Enrichment Analysis
2.6. Cell Culture and Reagents
2.7. Anchorage-Independent Growth Assay
2.8. Cell Growth Inhibition Assay
2.9. Western Blotting and Antibodies
2.10. RNAi Studies
2.11. Quantitative Real-Time PCR Analysis
3. Results
3.1. Whole Transcriptome Analysis Identified a Subset of Genes That Are Significantly Modulated by Cetuximab Treatment in Xenograft Mouse Tumors Induced by KRASG12D Mutation-Bearing LS174T CRC Cells
3.2. TNS4 is Significantly Downregulated by Cetuximab Treatment in a Subset of CRC Cell Lines
3.3. TNS4 Expression Is Associated with Oncogenic Potential of Colon Cancer Cell Lines
3.4. TNS4 Expression Is Regulated by MAP Kinase Pathway at a Transcriptional Level
3.5. Combinatorial Treatment with Selumetinib Increases the Sensitivity of Cetuximab in a Subset of KRAS Mutation-Bearing Colorectal Cancer Cell Lines
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Kim, S.; Kim, N.; Kang, K.; Kim, W.; Won, J.; Cho, J. Whole Transcriptome Analysis Identifies TNS4 as a Key Effector of Cetuximab and a Regulator of the Oncogenic Activity of KRAS Mutant Colorectal Cancer Cell Lines. Cells 2019, 8, 878. https://doi.org/10.3390/cells8080878
Kim S, Kim N, Kang K, Kim W, Won J, Cho J. Whole Transcriptome Analysis Identifies TNS4 as a Key Effector of Cetuximab and a Regulator of the Oncogenic Activity of KRAS Mutant Colorectal Cancer Cell Lines. Cells. 2019; 8(8):878. https://doi.org/10.3390/cells8080878
Chicago/Turabian StyleKim, Sujin, Nayoung Kim, Keunsoo Kang, Wonkyung Kim, Jonghwa Won, and Jeonghee Cho. 2019. "Whole Transcriptome Analysis Identifies TNS4 as a Key Effector of Cetuximab and a Regulator of the Oncogenic Activity of KRAS Mutant Colorectal Cancer Cell Lines" Cells 8, no. 8: 878. https://doi.org/10.3390/cells8080878