Related Experiment Video
Updated: Jul 15, 2026
10:43
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Oncogenic Ras drives EED degradation and PRC2 dysfunction to promote aggressive squamous cell carcinoma
Meng-Yen Li1, Aubrey Houser2,3, Pradeep Cheema4
1Department of Stem Cell Biology and Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nature Communications
|July 13, 2026
Summary
In squamous cell carcinomas (SCCs), oncogenic Ras signaling degrades the EED protein, leading to reduced H3K27me3 levels and aggressive tumors. Restoring EED reverses this epigenetic collapse, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Squamous cell carcinomas (SCCs) often show increased EZH2, linked to poor prognosis.
- EZH2 is part of Polycomb repressive complex 2 (PRC2), which marks DNA with H3K27me3.
- The precise role of PRC2 in SCC development was unclear.
Purpose of the Study:
- To investigate the function of PRC2 in SCC pathogenesis.
- To elucidate the mechanism linking oncogenic signaling to PRC2 activity in SCC.
- To explore therapeutic potential of targeting this pathway.
Main Methods:
- Analysis of human SCC samples and murine SCC models.
- Investigating the impact of oncogenic Ras signaling on PRC2 subunits.
- Assessing the effects of EED reintroduction on tumor growth and epigenetic marks.
Main Results:
- Despite elevated EZH2, human SCC and mouse models exhibit reduced H3K27me3.
- Oncogenic Ras signaling triggers EED degradation, destabilizing PRC2 and lowering H3K27me3.
- Loss of EED reprograms keratinocytes, promotes a pro-metastatic tumor microenvironment.
- Reintroducing EED halts tumor progression by restoring PRC2 and H3K27me3.
Conclusions:
- Oncogenic Ras signaling induces an epigenetic collapse in SCC by destabilizing PRC2 via EED degradation.
- This reprogramming drives tumor aggressiveness and metastasis.
- Restoring PRC2 integrity through EED reintroduction is a viable therapeutic strategy for epithelial cancers.
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