Title: XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin-mediated Rho-GDIβ mRNA stability.
Authors: Yu, Yonghui; Jin, Honglei; Xu, Jiheng; Gu, Jiayan; Li, Xin; Xie, Qipeng; Huang, Haishan; Li, Jingxia; Tian, Zhongxian; Jiang, Guosong; Chen, Caiyi; He, Feng; Wu, Xue-Ru; Huang, Chuanshu
Published In Int J Cancer, (2018 05 15)
Abstract: Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here, we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues. Knockdown of XIAP attenuated RhoGDIβ expression and reduced cancer cell invasion, whereas RhoGDIβ expression was attenuated in BBN-treated urothelium of RING-deletion knockin mice. Mechanistically, XIAP stabilized RhoGDIβ mRNA by its positively regulating nucleolin mRNA stability via Erks-dependent manner. Moreover, ectopic expression of GFP-RhoGDIβ in T24T(shXIAP) cells restored its lung metastasis in nude mice. Our results demonstrate that XIAP-regulated Erks/nucleolin/RhoGDIβ axis promoted BC invasion and lung metastasis.
PubMed ID: 29250796
MeSH Terms: Animals; Cell Line, Tumor; Female; HCT116 Cells; Humans; Inhibitor of Apoptosis Proteins/biosynthesis*; Inhibitor of Apoptosis Proteins/metabolism; Lung Neoplasms/genetics; Lung Neoplasms/metabolism; Lung Neoplasms/secondary*; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplasm Invasiveness; Phosphoproteins/metabolism*; RNA, Messenger/genetics; RNA, Messenger/metabolism*; RNA-Binding Proteins/metabolism*; Urinary Bladder Neoplasms/genetics; Urinary Bladder Neoplasms/metabolism; Urinary Bladder Neoplasms/pathology*; X-Linked Inhibitor of Apoptosis Protein/biosynthesis*; X-Linked Inhibitor of Apoptosis Protein/metabolism; rho Guanine Nucleotide Dissociation Inhibitor beta/genetics*; rho Guanine Nucleotide Dissociation Inhibitor beta/metabolism