Autor: |
Raffaella De Paolo, Samanta Sarti, Sara Bernardi, Francesco Cucco, Andrea Tavosanis, Letizia Pitto, Laura Poliseno |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Cell & Bioscience, Vol 13, Iss 1, Pp 1-5 (2023) |
Druh dokumentu: |
article |
ISSN: |
2045-3701 |
DOI: |
10.1186/s13578-023-01064-w |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
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