Enhancement of Migration and Invasion of Gastric Cancer Cells by IQGAP3

Biomolecules

Yusuke Nakamura¹  Yoichi Furukawa²  Jisnuson Svasti³  Pichaya Chanpanitkitchote⁴  Natini Jinawath⁵  Meng-Shin Shiao⁶ 

[1] Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan;Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan;Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand;Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;

关键词: IQGAP3;    gastric cancer;    oncogene;    migration;    invasion;    cytokinesis;   

DOI  :  10.3390/biom10081194

来源: DOAJ

【 摘 要 】

Although gastric cancer is one of the most common causes of cancer death in the world, mechanisms underlying this type of tumor have not been fully understood. In this study, we found that IQGAP3, a member of the IQGAP gene family, was significantly up-regulated in human gastric cancer starting from the early stages of tumor progression. Overexpression of IQGAP3 in 293T and NIH3T3 cells, which have no endogenous IQGAP3 expression, resulted in morphological change with multiple dendritic-like protrusions and enhanced migration. Overexpression of IQGAP3 also led to reduced cell–cell adhesion in 293T cells, likely as a result of its interactions with e-cadherin or β-catenin proteins. Additionally, IQGAP3 accumulated along the leading edge of migrating cells and at the cleavage furrow of dividing cells. In contrast, suppression of IQGAP3 by short-interfering RNA (siRNA) markedly reduced invasion and anchorage-independent growth of MKN1 and TMK-1 gastric cancer cells. We further confirmed that IQGAP3 interacted with Rho family GTPases, and had an important role in cytokinesis. Taken together, we demonstrated that IQGAP3 plays critical roles in migration and invasion of human gastric cancer cells, and regulates cytoskeletal remodeling, cell migration and adhesion. These findings may open a new avenue for the diagnosis and treatment of gastric cancer.

【 授权许可】

Unknown