Molecular Mechanisms of Collective Migration of Cancer Cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26640074
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Nagoya University
• Principal Investigator: Takahashi Masahide 名古屋大学, 医学(系)研究科(研究院), 教授 (40183446)
• Co-Investigator(Kenkyū-buntansha): KATO TAKUYA 名古屋大学, 大学院医学系研究科, 特任助教 (00551970)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: がん細胞 / 集団的移動 / 細胞接着因子 / TRIM27 / MTRF-B / Girdin / インテグリン / N-カドヘリン

Outline of Final Research Achievements

For collective invasion, cancer cells form cohesive groups comprised of leading cells (LCs) at the forefront and following cells (FCs) at the rear. However, the molecular mechanisms that define LCs and FCs remain elusive. We demonstrated that LCs, but not FCs, upregulated the expression of integrin β1. The LC-specific expression of integrin β1 was regulated by the TRIM27/MRTF-B complex in response to the loss of intercellular adhesion. Depletion of TRIM27 and MRTF-B abrogated the upregulation of integrin β1 in LCs and blocked the invasion of cancer cell groups in vitro and in vivo.
Girdin is an actin-binding protein that has multiple functions in postnatal neural development and cancer progression. Girdin is a regulator of collective (or chain) migration for neuroblasts born from neural stem cells in the subventricular zone. Girdin mutant mice showed an aberrant expression pattern of N-cadherin in migrating SVZ neuroblasts, leading to abrogation of neuroblast collective migration.

Free Research Field

実験病理学