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Series GSE138296 Query DataSets for GSE138296
Status Public on May 12, 2020
Title Cooperation of MYC and b-catenin in liver tumorigenesis requires Yap/Taz
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary One of the transcriptional targets of b-catenin/TCF and a key downstream effector of the WNT/b-catenin pathway in several tissues is the MYC proto-oncogene, which encodes for a transcription factor that is a master regulator of proliferation- and growth-related genes. However, several evidences indicate that this epistatic relationship does not seem to occur in liver: indeed Myc was not induced upon b-catenin activation driven by APC loss, and Myc deletion in hepatocytes does not suppress the effects of APC loss on cell proliferation and liver zonation. Besides, there are indications that the two pathways can be independently activated, and cooperate during tumorigenesis. In particular, MYC amplification and b-catenin mutations showed a tendency toward co-occurrence in either adult HCC or aggressive childhood hepatoblastoma, and MYC-driven HCC in experimental mouse models frequently acquired activating mutations in b-catenin. In order to address whether these observations reflect a functional cross-talk between the two pathways that may occur in a specific molecular subgroup of HCC patients, we generated a new mouse model allowing conditional activation of MYC and -catenin in hepatocytes. This model demonstrated a strong cooperativity between the two oncogenes in promoting liver tumorigenesis. Our data indicate that this cooperation occurs mainly through unrestrained proliferation of liver cells that requires the activity of the transcriptional co-factors Yap and Taz.
Overall design Total RNA profiling of gene expression upon short term activation of MYC and/or b-catenin in hepatocytes by AAV8-TBG-CRE injection or in Myc or Myc/b-catenin driven mouse hepatocellular carcinomas
Contributor(s) Bisso A, Filipuzzi M
Citation(s) 31965581
Submission date Oct 02, 2019
Last update date Jul 30, 2020
Contact name Marco Filipuzzi
Organization name IEO
Street address Via Giuseppe Ripamonti, 435
City Milan
ZIP/Postal code 20141
Country Italy
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (33)
GSM4104639 Tum_MYC_198825
GSM4104640 Tum_MYC_205931
GSM4104641 Tum_MYC_207155
BioProject PRJNA575356
SRA SRP223954

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Supplementary file Size Download File type/resource
GSE138296_RNASeq_RPKM_DESeq.txt.gz 6.3 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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