Inhibition of cell death in head and neck cancer cells
Initial Award Abstract
Cancers originating in the head and neck are directly related to tobacco use and represent the sixth most frequent cancer worldwide. An estimated 900,000 new cases are diagnosed each year and treatment options are limited to surgery and radiation. Although these approaches can control early stage disease, advanced disease is frequently incurable and fatal.
For their survival, cells rely on signals from proteins called receptors that form channels of communication between the external milieu and the cells’ internal environment. Cancer cells often overexpress many different kinds of receptors thereby gaining a survival advantage. We have shown that EphB4 is one such cell surface protein that is frequently overexpressed in head and neck cancers and provides survival signal to the cancer cells. Understanding the mechanisms by which this protein promotes survival, and turning off the function of this protein may lead to novel approaches to treat head and neck cancer.
Our preliminary results suggest that expression of EphB4 protein renders cells less sensitive to damage by the usual death signals that strictly control cell multiplication and survival. As part of this application, we propose to study the interaction between EphB4 and the death pathways to ascertain if artificially increasing or decreasing EphB4 levels will respectively decrease or increase the sensitivity to a particular death pathway. We seek to evaluate if EphB4 interrupts death signals by hindering recognition of death-inducing proteins by their receptors on the cell surface and/or by altering the levels of proteins within the cells that regulate cell death.
Our study is the first attempt to elucidate the role of EphB4 in providing survival advantage to tumor cells by studying the interaction between EphB4 and death pathways. Successful completion of this study will provide a strong rationale to pursue EphB4 as a novel target for biological therapy of head and neck cancer. |
|Receptor tyrosine kinase EphB4 is a survival factor in breast cancer
|Periodical: American Journal of Pathology
|Authors: Ram Kunmar Subramanyan