CBX5: A Potential Biomarker of Head and Neck Squamous Cell Carcinoma
Dr. Colleen L. Doci
Medicine and Health Sciences
Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common cancers in the world, and even in developed countries like the United States, the five-year survival is only 65%. This already low survival rate drops precipitously for metastatic disease, but unlike other malignancies, even regional spread significantly decreases 5-year survival. Despite its devastating impact on patient outcomes, conventional modalities to detect local micrometastases in oral cancer are inadequate and often debilitat-ing. Therefore, it is critical to identify more accurate means of predicting metastasis from the primary tumor. Oral cancer is unique in its ability to maintain intratumoral vasculature and several studies have linked increased intratumoral vascularity with in-creased risk of metastasis in oral cancer. However, immunohistochemical analysis of microvessel density alone is insufficient to predict the metastatic propensity of the tumor accurately. As an alternative, it may be possible instead to identify the molecular drivers of this vascularized phenotype and provide a more robust statistical risk assessment. Using an in vivo model of oral cancer metastasis, we have identified Chro-mobox 5 (CBX5) as a putative regulator of intratumoral vascularity and downstream metastasis. CBX5 is an epigenetic regulator that is mainly associated with chromatin remodeling and heterochromatin formation. Loss of CBX5 has been associated with more aggressive tumor types, suggesting that it may epigenetically regulate the tumor microenvironment. Indeed, CBX5 expression is significantly increased in avascular metastatic oral cancer cells compared to those cells that give rise to a vascular tumor phenotype in vivo. We have further hypothesized that overexpressing CBX5 will inhibit the in vitro metastatic phenotype of these cells. We will differentially regulate CBX5 expression in these cells through knockdown and overexpression and subsequently examine their migration, invasion, and motility in vitro. By confirming a mechanistic role for CBX5 in the regulation of a vascularized, metastatic phenotype, we will contribute to the development of a minimally invasive and reliable diagnostic technique that can improve outcomes for oral cancer patients.
Copyright 2019 all authors
Zemkewicz, John and Doci, Colleen Ph.D, "CBX5: A Potential Biomarker of Head and Neck Squamous Cell Carcinoma" (2019). MU-COM Research Day. 144.