Histone ubiquitination and epigenetic misregulation in skin cancer

Epigenetic misregulation and loss of cellular identity are common features of many cancers. One evolutionarily conserved group of epigenetic regulators that safeguard cellular identity and repeatedly implicated in various cancers is the Polycomb group proteins. However, Polycomb activity is intricate and provided by two different complexes, Polycomb repressive complex 1 (PRC1) and PRC2, which can operate together or separately through diverse mechanisms. Here, we focus on the role of PRC1 in cutaneous squamous cell carcinoma (cSCC) – the most prevalent form of skin cancer with metastatic potential. Our analysis uncovered major changes of PRC1-mediated histone H2AK119 mono-ubiquitination (H2AK119ub) in cSCC, and demonstrated that genetic ablation of PRC1 activity in the murine skin results in epidermal hyperplasia with early signs of malignant transformation. At the molecular level, we showed that PRC1 binds to and directly regulates oncogenic factors and molecular pathways known to be involved in cSCC, suggesting for a role of PRC1 in cSCC tumorigenesis. Identifying new roles for PRC1 and H2AK119ub in oncogenic processes can provide new treatment modalities for the treatment of cSCC, and will open new avenues for cancer research.