Cis-regulation in head and neck squamous cell carcinoma (HNSCC): implications for new therapies

Gill, Harmeet Kaur (2019). Cis-regulation in head and neck squamous cell carcinoma (HNSCC): implications for new therapies. University of Birmingham. Ph.D.

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Abstract

HNSCC is the sixth most common cancer in the world and over the last decade its genetic landscape has been extensively investigated. However, due to the heterogenic nature of HNSCC tumours, which is complicated by HPV infection, the effectiveness of current therapies and the development of new therapies have been hindered.

In this thesis, by using a combination of genome-wide methods, the cis-regulatory network was investigated in HNSCC cell lines and compared to non-tumourigenic primary oral cells. The analyses revealed a common core regulatory network shared by both the HNSCC and non-tumourigenic cells. The network included pathways, which have previously been found to promote HNSCC such as the EGFR, MAPK, TGF-b and WNT pathways. A novel finding was the involvement of the Hippo pathway and its transcription factor effector, TEAD4. The network appears to be driven primarily by the p63-AP1-TEAD4 transcription factors and in conjunction with the mentioned pathways, appears to form the underlying network required for epithelial function but also holds the potential to become deregulated, leading to HNSCC. Disruption of Hippo-driven gene transcription can reduce HNSCC cell viability therefore pointing to potential therapeutic targets and mechanisms to elucidate HNSCC function.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):