The potential role of YAP in head and neck squamous cell carcinoma

Abstract

Head and neck cancer: Protein dysfunction may give cancer the edge Abnormal activity of a protein involved in cell proliferation may influence the progression of head and neck cancers. Head and neck squamous cell carcinoma (HNSCC) affects the skin, throat, mouth and nose tissues. Disruption to the Hippo-YAP signaling pathway, which plays a key role in cell proliferation and differentiation, is implicated in multiple cancers. Joon Kim and Eunbie Shin at the Korea Advanced Institute of Science and Technology, Daejeon, South Korea, reviewed recent research into the role of YAP in HNSCC. Abnormal YAP protein activity triggers the expression of genes that encourage cancer cell proliferation. Mice with over-expressed YAP showed tissue overgrowth and tumor formation. High YAP levels have been found at the invasive front of HNSCC tumors, suggesting a role in metastasis. Further research is needed to verify whether YAP is a potential therapeutic target. The transcriptional cofactor YAP and its inhibitory regulators, Hippo kinases and adapter proteins, constitute an evolutionarily conserved signaling pathway that controls organ size and cell fate. The activity of the Hippo-YAP pathway is determined by a variety of intracellular and intercellular cues, such as cell polarity, junctions, density, mechanical stress, energy status, and growth factor signaling. Recent studies have demonstrated that YAP can induce the expression of a set of genes that allow cancer cells to gain a survival advantage and aggressive behavior. Comprehensive genomic studies have revealed frequent focal amplifications of theYAPlocus in human carcinomas, including head and neck squamous cell carcinoma (HNSCC). Moreover,FAT1, which encodes an upstream component of Hippo signaling, is one of the most commonly altered genes in HNSCC. In this review, we discuss the causes and functional consequences of YAP dysregulation in HNSCC. We also address interactions between YAP and other oncogenic drivers of HNSCC.