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| Status |
Public on Jan 01, 2019 |
| Title |
Expression alterations induced by restoration of AXIN1 expression in SNU449 hepatocellular carcinoma cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aberrant activation of Wnt/β-catenin signaling is observed in numerous cancers. In hepatocellular carcinoma activating mutations in CTNNB1 (20-25%) or loss of function mutations in AXIN1 (10%), AXIN2 (2%) and APC (1-2%) are observed. All these mutations lead to aberrant stabilization of β-catenin, which constitutively activates downstream Wnt/β-catenin target genes and triggers a genetic program resulting in tumor formation. However, in relation to AXIN1 mutations some reports have challenged whether these indeed result in tumor growth by enhancing β-catenin signaling (e.g. PMID: 16964294, 29525529). Several alternative pathways have also been linked to AXIN1 (ENSG00000103126), such as TGFβ, SAPK/JNK, p53, YAP/TAZ and c-myc. To identify which one of these or other unknown signaling routes are linked to AXIN1, using CRISPR-Cas9 genome editing, we have successfully repaired the homozygous p.R712* AXIN1 mutation present in the SNU449 hepatocellular carcinoma cell line. Next, using RNA sequencing the RNA expression patterns of 3 independent repaired clones were compared with 3 clones retaining the AXIN1 mutation. Surprisingly, only 5 genes were significantly altered in the repaired clones, among which AXIN2, a well-established β-catenin target gene. Thus, this analysis leads to the surprising observation that a commonly observed mutation in a hepatocellular tumor suppressor gene, is associated with minimal alterations in gene expression, at least in the SNU449 cell line.
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| Overall design |
Comparison of 3 independent repaired SNU449 clones with 3 clones retaining the AXIN1 mutation
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| Contributor(s) |
Smits RR, Lui PP, van de Geer WW, van de Werken HH |
| Citation(s) |
33811251 |
| Submission date |
Aug 23, 2018 |
| Last update date |
Apr 13, 2021 |
| Contact name |
Ron Smits |
| E-mail(s) |
m.j.m.smits@erasmusmc.nl
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| Organization name |
Erasmus MC
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| Street address |
Wytemaweg 80
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| City |
Rotterdam |
| ZIP/Postal code |
3015 CN |
| Country |
Netherlands |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA487644 |
| SRA |
SRP158717 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119001_RAW.tar |
26.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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