ArticleCancer research2009
RAS mutations affect tumor necrosis factor-induced apoptosis in colon carcinoma cells via ERK-modulatory negative and positive feedback circuits along with non-ERK pathway effects.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer.Cell death and differentiation · 2015Trial
- Cellular context alters EGF-induced ERK dynamics and reveals potential crosstalk with GDF-15.Biomicrofluidics · 2022Article
- Correlation and prognostic implications of intratumor and tumor draining lymph node Foxp3BMC gastroenterology · 2022Article
- Screening of core genes and pathways in breast cancer development via comprehensive analysis of multi gene expression datasets.Oncology letters · 2019Article
- Dual-specificity MAP kinase phosphatases in health and disease.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Inhibition of colon cancer growth by docosahexaenoic acid involves autocrine production of TNFα.Oncogene · 2016Article
- TNF-insulin crosstalk at the transcription factor GATA6 is revealed by a model that links signaling and transcriptomic data tensors.Science signaling · 2016Article
- Similar but different: distinct roles for KRAS and BRAF oncogenes in colorectal cancer development and therapy resistance.Oncotarget · 2015Review
- Multiscale analysis of the murine intestine for modeling human diseases.Integrative biology : quantitative biosciences from nano to macro · 2015Article
- How do oncoprotein mutations rewire protein-protein interaction networks?Expert review of proteomics · 2015Review
- Dual-specificity phosphatase 5 regulates nuclear ERK activity and suppresses skin cancer by inhibiting mutant Harvey-Ras (HRasQ61L)-driven SerpinB2 expression.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Role of ERK-MAPK signaling pathway in pentagastrin-regulated growth of large intestinal carcinoma.World journal of gastroenterology · 2014Article
- Differential gene expression of chemokines in KRAS and BRAF mutated colorectal cell lines: role of cytokines.World journal of gastroenterology · 2014Article
- Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Article
- Network analysis of differential Ras isoform mutation effects on intestinal epithelial responses to TNF-α.Integrative biology : quantitative biosciences from nano to macro · 2013Article
- Using partial least squares regression to analyze cellular response data.Science signaling · 2013Article
- Network quantification of EGFR signaling unveils potential for targeted combination therapy.Molecular systems biology · 2013Article
- Understanding resistance to combination chemotherapy.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2012Review
- Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium.PLoS biology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
More than 40% of colon cancers have a mutation in K-RAS or N-RAS, GTPases that operate as central hubs for multiple key signaling pathways within the cell. Utilizing an isogenic panel of colon carcinoma cells with K-RAS or N-RAS variations, we observed differences in tumor necrosis factor-alpha (TNFalpha)-induced apoptosis. When the dynamics of phosphorylated ERK response to TNFalpha were examined, K-RAS mutant cells showed lower activation whereas N-RAS mutant cells exhibited prolonged duration. These divergent trends were partially explained by differential induction of two ERK-modulatory circuits: negative feedback mediated by dual-specificity phosphatase 5 and positive feedback by autocrine transforming growth factor-alpha. Moreover, in the various RAS mutant colon carcinoma lines, the transforming growth factor-alpha autocrine loop differentially elicited a further downstream chemokine (CXCL1/CXCL8) autocrine loop, with the two loops having opposite effects on apoptosis. Although the apoptotic responses of the RAS mutant panel to TNFalpha treatment showed significant dependence on the respective phosphorylated ERK dynamics, successful prediction across the various cell lines required contextual information concerning additional pathways including IKK and p38. A quantitative computational model based on weighted linear combinations of these pathway activities successfully predicted not only the spectrum of cell death responses but also the corresponding chemokine production responses. Our findings indicate that diverse RAS mutations yield differential cell behavioral responses to inflammatory cytokine exposure by means of (a) differential effects on ERK activity via multiple feedback circuit mechanisms, and (b) differential effects on other key signaling pathways contextually modulating ERK-related dependence.
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