Functional analysis of Girdin family proteins in psyco-neurological disease and cancer

Abstract

Researchers around the world are searching for new possible targets and therapeutic options to help improve survival rates and develop cures for cancer. At Nagoya University Graduate School of Medicine, the Department of Pathology is conducting cutting-edge research into a number of key cancer types including, lung cancer, pancreatic cancer, brain cancer and thyroid cancer. Researchers, including Professor Masahide Takahashi, are studying the mechanisms of cancer progression by examining in detail some of the critical molecules involved in the process. Takahashi's team is particularly focused on the regulation of cell motility, as cell migration is involved in a number of biological processes such as cancer invasion into surrounding tissues, metastasis, angiogenesis and neurogenesis. He believes that by gaining a better understanding of how the motility of each cell type is controlled and how this control process becomes abnormal, we may discover new targets to pursue therapeutic developments to control and eradicate cancer and other diseases involving cell migration. "Discovering the novel mechanisms of cancer invasion and metastasis could lead to the development of new therapeutic strategies to control the malignant behaviour of each cancer," states Takahashi. Takahashi has been studying ways in which to tackle cancer for over 20 years and began by looking into the growth factor receptor (GFR)-Akt signalling pathway, thought to be critical in the regulation of cell motility. Little was known about the pathway at the time and he sought to challenge the lack of research in this area. Takahashi's team is currently investigating the mechanisms of cancer progression by discovering and investigating critical molecules involved in tumour progression. Since their identification of girdin (girders of actin filament), an important Akt-binding protein that plays a key role in regulating cell motility, Takahashi and his team have demonstrated its role in breast cancer metastasis and angiogenesis, as well as highlighting its presence in lamellipodia formation (actin reorganisation). "In the past 15 years, we have discovered that girdin is one of the key regulators of cell motility that works downstream of Akt," he highlights. Using cell culture experiments and a variety of knock-out, conditional knock-out (KO) and knock-in engineered mice, the team were able to highlight the importance of girdin in nervous system development as published in Neuron in 2009. "Girdin KO mice show abnormalities of the hippocampus and olfactory bulb that result from migration defects in neuronal cells," explains Takahashi.