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Yes Associated Protein Plays an Essential Role in the Development and Progression of Head and Neck Squamous Cell Carcinoma

  • Author(s): Bae, David
  • Advisor(s): Wang, Cun-Yu
  • et al.
Abstract

The intricate anatomy of the primary tumor, the occurrence of late-stage diagnosis, combined with the aggressive nature of head and neck squamous cell carcinoma (HNSCC) has made this disease difficult to treat. The global rate of HNSCC continues to rise, accounting up to 25% of all new cancer cases. But despite advances in treatment, the five year survival rate has remained stagnant for decades. Therefore a clearer understanding of the formation and progression of HNSCC is essential to the development of better therapeutic approaches to prevent and treat HNSCC patients. Recent studies have identified yes associated protein (YAP) as a potential target. YAP is a highly conserved transcriptional coactivator and has been found amplified as well as its expression upregulated and active in HNSCCs. In this study we hypothesize that YAP plays a key role in the development and progression of HNSCC. Our results show that activated YAP can transform and induce epithelial to mesenchymal transition (EMT) of our immortalized but nontransformed oral keratinocyte cell line OKF6 as seen by its ability to increase proliferation, saturation density, invasion, and induce anchorage independent growth. Moreover activated YAP potently enhances tumor formation and growth in vivo. YAP knockdown in HNSCC cell lines corroborated our initial findings where YAP knockdown could inhibit proliferation and invasion of HNSCC. We also discovered that YAP abundance correlated with tumor stage and lymph node metastasis in human HNSCC tissue samples. More recent studies have identified YAP regulation in response to extracellular cues. Therefore we further pursued our findings to determine whether YAP could mediate HGF induced cancer characteristics. We found that YAP knockdown could inhibit HGF induced proliferation and invasion of HNSCC, and by further microarray analysis, identified new potential targets and pathways by which YAP could direct cancer development and progression. Taken together our study not only suggests that YAP may play an important role in HNSCC, but also mediate response upon HGF stimulation to provide us with greater insight into the molecular regulation of HNSCC.

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