Dominant-negative Rac increases both inherent and ionizing radiation-induced cell migration in C6 rat glioma cells

✍ Scribed by So-Young Hwang; Jae-Won Jung; Jae-Seob Jeong; Yun-Jung Kim; Eok-Soo Oh; Tae-Hyun Kim; Joo-Young Kim; Kwan-Ho Cho; Inn-Oc Han

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 784 KB
• Volume: 118
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.21574

✦ Synopsis

Abstract

Rho‐like GTPases, including Cdc42, Rac1 and RhoA, regulate distinct actin cytoskeleton changes required for cell adhesion, migration and invasion. In the present study, we examined the role of Rac signaling in inherent migration, as well as radiation‐induced migration, of rat glioma cells. Stable overexpression of dominant‐negative Rac1N17 in a C6 rat glioma cell line (C6‐RacN17) promoted cell migration, and ionizing radiation further increased this migration. Migration was accompanied by decreased expression of the focal adhesion molecules FAK and paxillin. Focal contacts and actin stress fibers were also reduced in C6‐RacN17 cells. Downstream effectors of Rac include JNK and p38 MAP kinases. Irradiation transiently activated p38, JNK and ERK1/2 MAP kinases in C6‐RacN17 cells, while p38 and JNK were constitutively activated in C6 control cells. Blocking JNK activity with JNK inhibitor SP600125 inhibited migration, suggesting that the JNK pathway may regulate radiation‐induced, as well as inherent, migration of C6‐RacN17 cells. Additionally, the radiation‐induced migration increase was also inhibited by SB203580, a specific inhibitor of p38 MAP kinase. However, PD98059, a MEK kinase 1 inhibitor, failed to influence migration. This is the first evidence that suppression of Rac signaling may be involved in invasion or metastasis of glioma cells before and/or after radiotherapy. These data further suggest that radiotherapy for malignant glioma needs to be used with caution because of the potential for therapy‐induced cell migration or invasion and that pharmacological inhibition of cell migration and invasion through targeting the Rac signaling pathway may represent a new approach for improving the therapeutic efficacy of radiotherapy for malignant glioma. © 2005 Wiley‐Liss, Inc.