Fukushima Medical Univ. team pins down factor in cancer cell growth, provides clue for new drugs

In a world first, a team of researchers at the Department of Anatomy and Histology of Fukushima Medical University's School of Medicine has discovered a mechanism to restrict cancer cell growth by halting the activity of activator protein-1 (AP-1) transcription factors in small cancer cell vesicles called endosomes. The university announced on Dec. 2 that it is possible to slow the growth of cancer cells by creating a condition in which AP-1 cannot function, raising hopes for the development of a new cutting-edge drug to treat cancer. The research group has discovered that AP-1 in endosomes functions to regulate the lifespan of the epidermal growth factor receptor (EGFR) that causes cells to grow abnormally. Cancer cells that proliferate easily contain higher levels of AP-1 than those that do not, thus making them unable to suppress EGFR recycling back to cell membranes. The team probed the condition of cells among patients with lung, hepatocellular and large intestine cancer -- 131 in total -- and compared each patient's cancerous and noncancerous regions. It found the activity of AP-1 was significantly higher in cancerous regions in about 70% of patients. EGFR, a molecule important for normal cell growth, is also known as one of the causes of cancer and a major study subject for experts worldwide. But research focusing on protein lifespans is rare, leaving previously unknown the factor that determines EGFR inactivation. In treatment using anticancer agents, there exists the risk of cancer cells acquiring drug resistance and growing again. Therefore, it is considered necessary to develop drugs based on different mechanisms. The study team believes the latest outcome will be helpful in developing new drugs. The research was led by Associate Professor Takefumi Uemura, 41, and Professor Satoshi Waguri, 57, of the university. Their research paper was published by a British medical science journal. ==Kyodo