title: X-linked inhibitor of apoptosis protein (XIAP) mediates cancer cell motility via Rho GDP dissociation inhibitor (RhoGDI)-dependent regulation of the cytoskeleton.
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.
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Liu
authors.forename: Dongyun
authors.initials: D
authors.lastname: Zhang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Luo
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Yu
authors.forename: Jianxiu
authors.initials: J
authors.lastname: Yu
authors.forename: Jingxia
authors.initials: J
authors.lastname: Li
authors.forename: Xinhai
authors.initials: X
authors.lastname: Zhang
authors.forename: Baolin
authors.initials: B
authors.lastname: Zhang
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Chen
authors.forename: Xue-Ru
authors.initials: XR
authors.lastname: Wu
authors.forename: Germán
authors.initials: G
authors.lastname: Rosas-Acosta
authors.forename: Chuanshu
authors.initials: C
authors.lastname: Huang
mesh_terms: D000199:Actins; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017434:Protein Structure, Tertiary; D058207:Sumoylation / Q000235:genetics; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: C569638:ARHGDIA protein, human; D000199:Actins; D020730:Guanine Nucleotide Dissociation Inhibitors; D009363:Neoplasm Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors