PUBLICATION
Differential impact of BRAFV600E isoforms on tumorigenesis in a zebrafish model of melanoma
- Authors
- De Paolo, R., Sarti, S., Bernardi, S., Cucco, F., Tavosanis, A., Pitto, L., Poliseno, L.
- ID
- ZDB-PUB-230702-36
- Date
- 2023
- Source
- Cell & Bioscience 13: 121121 (Journal)
- Registered Authors
- Keywords
- 3?UTR, BRAFV600E-X1, BRAFV600E-ref, Melanoma modeling, Zebrafish
- MeSH Terms
- none
- PubMed
- 37393328 Full text @ Cell Biosci.
Citation
De Paolo, R., Sarti, S., Bernardi, S., Cucco, F., Tavosanis, A., Pitto, L., Poliseno, L. (2023) Differential impact of BRAFV600E isoforms on tumorigenesis in a zebrafish model of melanoma. Cell & Bioscience. 13:121121.
Abstract
BRAFV600E comes as two main splicing variants. The well-studied ref isoform and the recently discovered X1 isoform are co-expressed in cancer cells and differ in terms of 3'UTR length and sequence, as well as C-term protein sequence. Here, we use a melanoma model in zebrafish to study the role played by each isoform in larval pigmentation, nevi formation, and their progression into melanoma tumours. We show that both BRAFV600E-ref and BRAFV600E-X1 proteins promote larval pigmentation and nevi formation, while melanoma-free survival curves performed in adult fish indicate that BRAFV600E-ref protein is a much stronger melanoma driver that BRAFV600E-X1 protein. Crucially, we also show that the presence of the 3'UTR suppresses the effect of ref protein. Our data highlight the necessity to undertake a systematic study of BRAFV600E isoforms, in order to uncover the full spectrum of their kinase-(in)dependent and coding-(in)dependent functions, hence to develop more informed strategies for therapeutic targeting.
Genes / Markers
Figure Gallery (1 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping