Radioresistance is a major cause of treatment failure and relapse in head and neck squamous cell carcinoma (HNSCC). Novel molecular targets need to be identified to increase cure rates and radiosensitivity in HNSCC. The MET receptor tyrosine kinase is highly dysregulated in cancer and plays a role in tumourigenesis, chemoresistance, and radioresistance. However, the role of MET in HNSCC radioresistance has not yet been investigated and may potentially be a radiosensitizing target.
We discovered MET expression and intact ligand-induced signalling in HNSCC cell lines. Small molecule MET kinase inhibitors inhibited ligand-induced MET activation and downstream signalling. These inhibitors decreased HNSCC cell proliferation and clonogenic survival. Similarly, short-interfering RNAs targeting MET also decreased cell proliferation. The combination of radiation with the MET kinase inhibitors decreased clonogenic survival in an additive manner. Cell cycle analyses demonstrated that MET inhibitors alone or in combination with radiation induced small increases in sub-G1 cell populations.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32500 |
| Date | 23 July 2012 |
| Creators | Wu, Ronald |
| Contributors | Liu, Fei-Fei |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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