Author Response: ETS Family Transcriptional Regulators Drive Chromatin Dynamics and Malignancy in Squamous Cell Carcinomas

The study by Yang, Schramek et al. revealed that in squamous cell carcinoma stem cells (SCC-SCs), super-enhancers (SEs) were distinct from those in normal skin stem cells, with a unique set of genes highly expressed in cancer stem cells. The transcription factor ETS2 played a crucial role by binding to these SEs, reprogramming gene expression to promote cancer development, and was identified as a major driver of squamous cell carcinoma. The study found that ETS, SOX, and AP1 were key transcription factors in SCC-SCs, with ETS motifs present in approximately 80% of SCC-SEs. Overactive ETS2 increased the expression of genes linked to inflammation and cancer growth, and its knockdown reduced tumor growth, suggesting its potential as a therapeutic target. The findings highlighted a new regulatory network governing gene expression in cancer, underscoring the importance of SE-regulated genes and transcription factors in the progression and treatment of SCCs.