ZSCAN4 Induces the Pluripotency Pathway in Head and Neck Squamous Cell Carcinoma Cells

Abstract

Cancer cells and pluripotent stem cells possess the ability to proliferate, self-renew, evade normal cellular senescence, and achieve replicative immortality. Here, we investigate the role of ZSCAN4, a factor known for Its critical impact during early development. ZSCAN4 was considered a putative transcription factor due to its structural features. Previous data from our lab show that ZSCAN4 leads to increased cancer-stem cell frequency, thereby contributing to cancer cell immortality. Its mechanism of action is still not well understood. A previous study from our lab used human squamous cell carcinoma cells (Tu167) with or without ZSCAN4 overexpression followed by Next generation sequencing (Next-Gen ChIP-seq). In this study, we first used Reactome to assess the pathways affected by ZSCAN4. We were excited to learn that ZSCAN4 binds to the core pluripotency factors and most of the pluripotency-related genes. Therefore, we aligned our data using the genome analysis tool gEAR with additional data generated from ZSCAN4 overexpression or knockdown in mouse embryonic stem cells (ESCs). We used RNA-seq or ChIP-seq data to define the effect of ZSCAN4 on the pluripotency pathway. Finally, the data was validated by RT-quantitative polymerase chain reaction (RT-qPCR). Our novel data suggest that ZSCAN4 exerts its effect on pluripotency-like properties of cancer cells by binding and increasing histone acetylation at the promoters and enhancers of the core pluripotency factors, as well as the downstream genes in the pluripotency pathway. Our data suggest that by interacting with these regulatory elements, ZSCAN4 enhances chromatin accessibility and increases cancer stem cell-related properties. Our research supports the critical role of ZSCAN4 in linking the pluripotency pathway and cancer stemness.