Please use this identifier to cite or link to this item:
https://doi.org/10.1186/s13073-017-0511-4
DC Field | Value | |
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dc.title | Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genomewide forward genetic screen in human colorectal cancer cells | |
dc.contributor.author | Kundu, S | |
dc.contributor.author | Ali, M.A | |
dc.contributor.author | Handin, N | |
dc.contributor.author | Padhan, N | |
dc.contributor.author | Larsson, J | |
dc.contributor.author | Karoutsou, M | |
dc.contributor.author | Ban, K | |
dc.contributor.author | Wisniewski, J.R | |
dc.contributor.author | Artursson, P | |
dc.contributor.author | He, L | |
dc.contributor.author | Hellström, M | |
dc.contributor.author | Sjöblom, T | |
dc.date.accessioned | 2020-10-20T05:10:31Z | |
dc.date.available | 2020-10-20T05:10:31Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Kundu, S, Ali, M.A, Handin, N, Padhan, N, Larsson, J, Karoutsou, M, Ban, K, Wisniewski, J.R, Artursson, P, He, L, Hellström, M, Sjöblom, T (2018). Linking FOXO3, NCOA3, and TCF7L2 to Ras pathway phenotypes through a genomewide forward genetic screen in human colorectal cancer cells. Genome Medicine 10 (1) : 2. ScholarBank@NUS Repository. https://doi.org/10.1186/s13073-017-0511-4 | |
dc.identifier.issn | 1756994X | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/178120 | |
dc.description.abstract | Background: The Ras pathway genes KRAS, BRAF, or ERBBs have somatic mutations in ~ 60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack mutations activating the Ras pathway or whether they have acquired mutations in genes hitherto unknown to belong to the pathway. Methods: To address the second possibility and extend the compendium of Ras pathway genes, we used genomewide transposon mutagenesis of two human colorectal cancer cell systems deprived of their activating KRAS or BRAF allele to identify genes enabling growth in low glucose, a Ras pathway phenotype, when targeted. Results: Of the 163 recurrently targeted genes in the two different genetic backgrounds, one-third were known cancer genes and one-fifth had links to the EGFR/Ras/MAPK pathway. When compared to cancer genome sequencing datasets, nine genes also mutated in human colorectal cancers were identified. Among these, stable knockdown of FOXO3, NCOA3, and TCF7L2 restored growth in low glucose but reduced MEK/MAPK phosphorylation, reduced anchorage-independent growth, and modulated expressions of GLUT1 and Ras pathway related proteins. Knockdown of NCOA3 and FOXO3 significantly decreased the sensitivity to cetuximab of KRAS mutant but not wild-type cells. Conclusions: This work establishes a proof-of-concept that human cell-based genome-wide forward genetic screens can assign genes to pathways with clinical importance in human colorectal cancer. © The Author(s). 2018. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | cetuximab | |
dc.subject | epidermal growth factor receptor | |
dc.subject | glucose | |
dc.subject | glucose transporter 1 | |
dc.subject | mitogen activated protein kinase | |
dc.subject | mitogen activated protein kinase kinase | |
dc.subject | Ras protein | |
dc.subject | transcription factor 7 like 2 | |
dc.subject | transcription factor FKHRL1 | |
dc.subject | cetuximab | |
dc.subject | FOXO3 protein, human | |
dc.subject | glucose transporter 1 | |
dc.subject | mitogen activated protein kinase | |
dc.subject | NCOA3 protein, human | |
dc.subject | Ras protein | |
dc.subject | SLC2A1 protein, human | |
dc.subject | small interfering RNA | |
dc.subject | steroid receptor coactivator 3 | |
dc.subject | TCF7L2 protein, human | |
dc.subject | transcription factor 7 like 2 | |
dc.subject | transcription factor FKHRL1 | |
dc.subject | anchorage independent growth | |
dc.subject | Article | |
dc.subject | cancer growth | |
dc.subject | colorectal cancer cell line | |
dc.subject | controlled study | |
dc.subject | drug sensitivity | |
dc.subject | enzyme phosphorylation | |
dc.subject | FOXO3 gene | |
dc.subject | gene | |
dc.subject | gene expression | |
dc.subject | gene knockdown | |
dc.subject | gene sequence | |
dc.subject | genetic screening | |
dc.subject | GLUT1 gene | |
dc.subject | mutagenesis | |
dc.subject | NCOA3 gene | |
dc.subject | oncogene K ras | |
dc.subject | phenotype | |
dc.subject | priority journal | |
dc.subject | TCF7L2 gene | |
dc.subject | transposon | |
dc.subject | wild type | |
dc.subject | cell proliferation | |
dc.subject | colorectal tumor | |
dc.subject | drug effect | |
dc.subject | drug resistance | |
dc.subject | gene expression regulation | |
dc.subject | genetic screening | |
dc.subject | genetics | |
dc.subject | human | |
dc.subject | human genome | |
dc.subject | metabolism | |
dc.subject | pathology | |
dc.subject | phenotype | |
dc.subject | phosphorylation | |
dc.subject | proteomics | |
dc.subject | signal transduction | |
dc.subject | tumor cell line | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Proliferation | |
dc.subject | Cetuximab | |
dc.subject | Colorectal Neoplasms | |
dc.subject | DNA Transposable Elements | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Extracellular Signal-Regulated MAP Kinases | |
dc.subject | Forkhead Box Protein O3 | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Gene Knockdown Techniques | |
dc.subject | Genetic Testing | |
dc.subject | Genome, Human | |
dc.subject | Glucose Transporter Type 1 | |
dc.subject | Humans | |
dc.subject | Nuclear Receptor Coactivator 3 | |
dc.subject | Phenotype | |
dc.subject | Phosphorylation | |
dc.subject | Proteomics | |
dc.subject | ras Proteins | |
dc.subject | RNA, Small Interfering | |
dc.subject | Signal Transduction | |
dc.subject | Transcription Factor 7-Like 2 Protein | |
dc.type | Article | |
dc.contributor.department | BIOCHEMISTRY | |
dc.description.doi | 10.1186/s13073-017-0511-4 | |
dc.description.sourcetitle | Genome Medicine | |
dc.description.volume | 10 | |
dc.description.issue | 1 | |
dc.description.page | 2 | |
Appears in Collections: | Elements Staff Publications |
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