Evaluation of SMPD3 as a quarterback for extracellular vesicle-mediated metastasis in oral carcinoma

Mouth cancer remains an under-studied and significant global cancer killer; dismal survival rates (~50% over 5 years) have not changed in decades. Potential spread to neck lymph nodes (metastasis) is the single most important prognostic factor but clinical assessment has not been very accurate. This results in insufficient surgery or over-treatment for many patients. A better understanding of mouth cancer and its way to spread is needed to improve treatment for the patients. The SMPD3 gene is frequently dysregulated in mouth cancer it has been linked to metastasis. SMPD3 expression can impact microRNA (miRNA: small non-coding RNA molecules that regulates gene expression) cargo within extracellular vesicles (EVs). Many of these miRNAs have been linked to tumor invasion and metastasis. I hypothesize that mouth cancer cells that exhibit decreased SMPD3 expression plays a role in lymph node metastasis via specific miRNA EV content and that SMPD3 expression can be used as a biological marker for lymph node spread in mouth cancer. We hope this project will lead to novel tools to identify the patients at highest risk for lymph node involvement, ultimately increasing survival rate and quality of life for mouth cancer patients.