Authors
Chen Khuan Wong, Dan Li, Tomer Itkin, Cindy J Lee, Nicholas A Teri, Jiasheng Zhou, Dana M Schoeps, Nikita R Staniloae, Mohini R Pachai, Makhzuna N Khudoynazarova, Priya Pancholi, Woo Hyun Cho, Gabriella Bayshtok, Kae Kristoff, Selina Fan, Richard Lin, Shahin Rafii, Benedikt Bosbach, Scott W Lowe, Cristina R Antonescu, Ping Chi, Yu Chen
Published in
bioRxiv : the preprint server for biology. Oct 09, 2026. Epub Oct 09, 2026.
Abstract
MYC amplification is the most common genetic alteration in radiation-associated angiosarcoma and is also present in a subset of de novo primary angiosarcoma, yet its oncogenic role in this vascular malignancy remains unclear. Here, we report that inducible, endothelial-specific MYC overexpression alone was sufficient to drive angiosarcomagenesis in mice. The resulting pulmonary angiosarcoma tumors exhibited impaired endothelial differentiation, indicative of MYC-driven lineage plasticity. Notably, MYC inactivation in dedifferentiated allografts induced growth arrest and restored endothelial gene expression, demonstrating MYC-dependent reversible cellular plasticity. Integrative analyses of MYC ChIP-seq, ATAC-seq, and RNA-seq revealed that overexpressed MYC preferentially occupied highly accessible promoters and activated genes involved in cell growth. Consistent with the murine findings, MYC -amplified human angiosarcomas were enriched for MYC target and cell-cycle programs and depleted of endothelial lineage signatures. MYC overexpression in human endothelial and angiosarcoma cells recapitulated these transcriptional changes, enhanced proliferation, and impaired endothelial tube formation. Together, our results establish MYC as an oncoprotein that promotes endothelial lineage plasticity to drive angiosarcoma initiation and progression.
PMID:
42926684
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.
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