Splicing control by PHF5A in melanoma

Abnormalities in alternative splicing are a hallmark of cancer formation. In this study, we investigated the role of the splicing factor PHD Finger Protein 5A (PHF5A) in melanoma progression. Malignant melanoma is the deadliest form of skin cancer, and patients with a high PHF5A expression show poor overall survival. We revealed that the loss of PHF5A leads to massive splicing defects of different tumor-relevant genes, highlighting the crucial role of PHF5A as a driver for melanoma malignancy. Additionally, we show that modulating this important cellular process leads to an increased rate of apoptosis by triggering FAS- as well as UPR-mediated apoptosis pathways in melanoma cells. These findings are tumor-specific since we were not able to observe these regulations in fibroblasts. Understanding the functional role of PHF5A and the underlying splicing network may also provide insights in identifying new therapeutic targets for this aggressive form of skin cancer.