Activated Hepatocyte growth factor receptor (MET) is frequently overexpressed and highly associated with head and neck squamous cell carcinoma (HNSCC) metastasis. However, little is known about the epigenetic regulation of the MET signaling pathway. In this study, we investigated the role of lysine-specific demethylase KDM6B and its underlying mechanism in HNSCC metastasis. KDM6B was knocked-down in growth factor-induced HNSCC cells and cells overexpressing oncogenic translocated promoter region MET (TPR-MET). A microarray was performed to identify the downstream targets of KDM6B that promote metastasis and both in vivo and in vitro studies were performed. We identified KDM6B as a key epigenetic regulator of MET-driven HNSCC invasion and metastasis in vitro and in vivo. Suppression of KDM6B decreased the expression of ETS proto-oncogene 1 (ETS1) and high mobility group AT-Hook 2 (HMGA2) genes, known as drivers of metastasis. Mechanistically, we found that histone demethylation by KDM6B facilitated the binding of the transcription factor ELK1 to the promoters of ETS1 and HMGA2. In a mouse model, KDM6B knockdown inhibited lymph node metastasis. Moreover, KDM6B expression was highly elevated in human SCC tissues with metastasis compared to both normal and SCC without lymph node metastasis. Our study provides insight into the epigenetic regulation of HNSCC invasion and metastasis and suggests that KDM6B could be an important therapeutic target for inhibiting invasive tumor growth and metastasis.
University of California, Los Angeles
2013 - Obtained DDS degree at the UCLA School of Dentistry, 2017 - Obtained PhD degree at UCLA from Dr. Cun-Yu Wang's lab on the subject of molecular biology and signaling of head and neck squamous cell carcinoma growth, progression, and metastasis, 2017 - started the endodontics residency program at UCLA School of Dentistry,
Thursday, April 26
10:00 AM – 1:00 PM