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| 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.
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| 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
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| |
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| Contributor(s) |
Bisso A, Filipuzzi M |
| Citation(s) |
31965581 |
| Submission date |
Oct 02, 2019 |
| Last update date |
Jul 30, 2020 |
| Contact name |
Marco Filipuzzi |
| E-mail(s) |
marco.filipuzzi@ieo.it
|
| Organization name |
IEO
|
| Street address |
Via Giuseppe Ripamonti, 435
|
| City |
Milan |
| ZIP/Postal code |
20141 |
| Country |
Italy |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (33)
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| Relations |
| BioProject |
PRJNA575356 |
| SRA |
SRP223954 |
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