Analysis of the relationship between the KRAS G12V oncogene and the Hippo effector YAP1 in embryonal rhabdomyosarcoma
| Autor: | Abdalla D. Mohamed, Simone Hettmer, Neil Vargesson, Henning Wackerhage, Nupur Shah |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Medicine Mice Transgenic Biology medicine.disease_cause Article Cell Line Proto-Oncogene Proteins p21(ras) 03 medical and health sciences medicine Animals Humans Rhabdomyosarcoma Embryonal Rhabdomyosarcoma lcsh:Science neoplasms Cyclin-Dependent Kinase Inhibitor p16 Adaptor Proteins Signal Transducing YAP1 Regulation of gene expression Multidisciplinary Oncogene Effector lcsh:R YAP-Signaling Proteins Oncogenes medicine.disease Phosphoproteins digestive system diseases Gene Expression Regulation Neoplastic 030104 developmental biology HEK293 Cells Cancer research lcsh:Q KRAS Embryonal rhabdomyosarcoma C2C12 Transcription Factors |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Persistent hyperactivity of the Hippo effector YAP in activated satellite cells is sufficient to cause embryonal rhabdomyosarcoma (ERMS) in mice. In humans, YAP is abundant and nuclear in the majority of ERMS cases, and high YAP expression is associated with poor survival. However, YAP1 is rarely mutated in human ERMS. Instead, the most common mutations in ERMS are oncogenic RAS mutations. First, to compare YAP1S127A and KRASG12V-driven rhabdomyosarcomas, we re-analysed gene expression microarray datasets from mouse rhabdomyosarcomas caused by these genes. This revealed that only 20% of the up or downregulated genes are identical, suggesting substantial differences in gene expression between YAP and KRAS-driven rhabdomyosarcomas. As oncogenic RAS has been linked to YAP in other types of cancer, we also tested whether KRAS G12V alone or in combination with loss of p53 and p16 activates YAP in myoblasts. We found that neither KRAS G12V alone nor KRAS G12V combined with loss of p53 and p16 activated Yap or Yap/Taz-Tead1–4 transcriptional activity in C2C12 myoblasts or U57810 cells. In conclusion, whilst oncogenic KRAS mutation might activate Yap in other cell types, we could find no evidence for this in myoblasts because the expression of KRAS G12V expression did not change Yap/Taz activity in myoblasts and there was a limited overlap in gene expression between KRAS G12V and YAP1 S127A-driven tumours. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|