Masahide Takahashi
Nagoya University Graduate School of Medicine, Japan
Title: Roles of Akt-girdin signaling in cancer progression
Biography
Biography: Masahide Takahashi
Abstract
Girdin is an actin-binding Akt substrate that plays an important role in actin organization and Akt-dependent cell motility in fibroblasts and cancer cells. Girdin is expressed in a variety of cancer cells including breast cancer cells and glioblastoma cells, and is phosphorylated by the stimulation of growth factors. Girdin knockdown markedly inhibited migration and invasion of cancer cells in vitro and in vivo. Recently, we found that Girdin is also expressed and activated by Akt phosphorylation in cancer-associated fibroblast (CAF) and blood vessels within the tumor microenvironment. We established a knock-in mouse line (designated SA mice) engineered to express a Girdin mutant that lacks the Akt phosphorylation site at serine 1416 (S1416A). The growth of allogeneic tumors (Lewis lung tumors) was decreased in SA mice compare with wild-type (WT) counterparts. Notably, the co-transplantation of tumor cells with either skin fibroblasts or CAF derived from　SA mice also attenuated tumor growth compared to co-transplantation with WT fibroblasts or CAF, indicating the in vivo relevance of Girdin phosphorylation in formation of the tumor microenvironment. Our results revealed a role for Akt-mediated Girdin phosphorylation in CAF during tumor progression, highlighting the need to inhibit Akt function in both tumor cells a CAF.
