Grant: Project Grant

The mouth is a unique environment, constantly exposed to bacteria, saliva, and the body's natural defense systems. These systems typically work in harmony to maintain our health. However, sometimes the cells that line the mouth (keratinocytes) undergo changes, known as oral dysplasia or potentially malignant lesions, which can, in some cases, progress to oral cancer. Oral cancer is a severe disease with high rates of illness and death. Finding better ways to predict and prevent the development of oral cancer is critical, and this application focuses on novel aspects related to oral cancer progression. Our research has identified a molecule called Fn14 that plays an important role in this process. We have discovered that Fn14 activity increases significantly as oral lesions progress toward cancer, both in human samples and in animal models. We believe Fn14 helps abnormal cells move and invade surrounding tissues, making it easier for cancer to develop. To test this idea, our project combines animal studies, laboratory experiments, and patient samples. In mice that lack Fn14, we will study whether cancer develops differently. In the laboratory, we will explore the chain of signals that cause Fn14 to rise and drive cell invasion. Finally, by analyzing tissue from patients with precancerous mouth lesions, we will determine whether higher levels of Fn14 predict which lesions are more likely to become cancer. If successful, this research will reveal a new biological pathway that contributes to the development of oral cancer. More importantly, it may provide health care providers with a way to identify patients at greater risk earlier, improving how we monitor, diagnose, and treat people with precancerous lesions in the mouth.