Title: X-linked inhibitor of apoptosis protein (XIAP) mediates cancer cell motility via Rho GDP dissociation inhibitor (RhoGDI)-dependent regulation of the cytoskeleton.
Authors: Liu, Jinyi; Zhang, Dongyun; Luo, Wenjing; Yu, Yonghui; Yu, Jianxiu; Li, Jingxia; Zhang, Xinhai; Zhang, Baolin; Chen, Jingyuan; Wu, Xue-Ru; Rosas-Acosta, Germán; Huang, Chuanshu
Published In J Biol Chem, (2011 May 06)
Abstract: X-linked inhibitor of apoptosis protein (XIAP) overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers. However, the molecular basis of XIAP in the regulation of cancer cell biological behavior remains largely unknown. In this study, we found that a deficiency of XIAP expression in human cancer cells by either knock-out or knockdown leads to a marked reduction in β-actin polymerization and cytoskeleton formation. Consistently, cell migration and invasion were also decreased in XIAP-deficient cells compared with parental wild-type cells. Subsequent studies demonstrated that the regulation of cell motility by XIAP depends on its interaction with the Rho GDP dissociation inhibitor (RhoGDI) via the XIAP RING domain. Furthermore, XIAP was found to negatively regulate RhoGDI SUMOylation, which might affect its activity in controlling cell motility. Collectively, our studies provide novel insights into the molecular mechanisms by which XIAP regulates cancer invasion and offer a further theoretical basis for setting XIAP as a potential prognostic marker and specific target for treatment of cancers with metastatic properties.
PubMed ID: 21402697
MeSH Terms: Actins; Cell Line, Tumor; Cell Movement*; Cytoskeleton/genetics; Cytoskeleton/metabolism*; Gene Knockdown Techniques; Guanine Nucleotide Dissociation Inhibitors/genetics; Guanine Nucleotide Dissociation Inhibitors/metabolism*; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism*; Neoplasms/genetics; Neoplasms/metabolism*; Neoplasms/pathology; Protein Structure, Tertiary; Sumoylation/genetics; X-Linked Inhibitor of Apoptosis Protein/genetics; X-Linked Inhibitor of Apoptosis Protein/metabolism*; rho Guanine Nucleotide Dissociation Inhibitor alpha; rho-Specific Guanine Nucleotide Dissociation Inhibitors