A team of NIH-funded scientists has developed a new method that changes the way genes are regulated to effectively cause cancer tumors to shrink and die in the laboratory. Supported in part by a Penn State University Clinical and Translational Science Institute (CTSI) pilot grant award and research funding from the National Cancer Institute (NCI), Penn State professors Yanming Wang and Gong Chen recently published work in the Journal of Biological Chemistry suggesting that stopping the action of an enzyme called PAD4 (peptidylarginine deiminase 4) sets off a chain reaction of “molecular switches” in cancer cells. The effect is to switch the internal cell signals from growth to death.
Funded in part by NIH’s Clinical and Translational Science Awards (CTSA) program, this multidisciplinary team, is hopeful that their discovery will aid in the development of anti-cancer drugs that only target cancerous tissue without damaging healthy cells and vital organs. Chemotherapy, a standard cancer treatment, damages both healthy and diseased cells. The studied anti-cancer drug has the potential to reduce or eliminate these side effects and improve chemotherapies for cancer patients.
PAD4 alters proteins called histones that package and regulate DNA in a process called “epigenetics,” which alters gene function without changing the DNA sequence. This process is often involved in activating and deactivating genes ― turning genes on and off. Interestingly, PAD4 has been found in concentrations greater than usual in numerous types of human cancers, such as breast and bone cancer. This PAD4 “overexpression” also appears to be involved in such autoimmune diseases as rheumatoid arthritis and multiple sclerosis. Wang and Chen are using cell cultures and mouse tumor models to explore the way excess PAD4 affects cells.