Promotion of Cancer Cell Migration

Fu, Ping; Thompson, Julian; Bach, Leon Ashley

doi:10.1074/jbc.m703066200

Cited by 60 publications

(27 citation statements)

References 56 publications

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“…Transcriptome analysis between NAC1-expressing SKOV3 human ovarian cancer cells and NAC1-siRNA silenced SKOV3 cells demonstrated that several genes differentially expressed by NAC1 were involved in cell migration [34]. These include forkhead box Q1 ( FOXQ1 ) [34], insulin-like growth factor-binding protein-6 ( IGFBP6 ) [35], chemokine (C-X-C motif) ligand 1 (CXCL1, also known as GROα) [36], drebrin-like protein ( DBNL , also known as mammalian actin-binding protein-1) [37], and Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) [38]. Further work will be required to define the precise nature of the signaling cascades linking NAC1 to these genes.…”

Section: Discussionmentioning

confidence: 99%

Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

et al. 2013

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NAC1 encoded by NACC1 is a member of the BTB/POZ family of proteins and participates in several pathobiological processes. However, its function during tissue development has not been elucidated. In this study, we compared homozygous null mutant Nacc1-/- and wild type Nacc1+/+ mice to determine the consequences of diminished NAC1 expression. The most remarkable change in Nacc1-/- mice was a vertebral patterning defect in which most knockout animals exhibited a morphological transformation of the sixth lumbar vertebra (L6) into a sacral identity; thus, the total number of pre-sacral vertebrae was decreased by one (to 25) in Nacc1-/- mice. Heterozygous Nacc1+/- mice had an increased tendency to adopt an intermediate phenotype in which L6 underwent partial sacralization. Nacc1-/- mice also exhibited non-closure of the dorsal aspects of thoracic vertebrae T10-T12. Chondrocytes from Nacc1+/+ mice expressed abundant NAC1 while Nacc1-/- chondrocytes had undetectable levels. Loss of NAC1 in Nacc1-/- mice was associated with significantly reduced chondrocyte migratory potential as well as decreased expression of matrilin-3 and matrilin-4, two cartilage-associated extracellular matrix proteins with roles in the development and homeostasis of cartilage and bone. These data suggest that NAC1 participates in the motility and differentiation of developing chondrocytes and cartilaginous tissues, and its expression is necessary to maintain normal axial patterning of murine skeleton.

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Section: Discussionmentioning

confidence: 99%

Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

et al. 2013

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“…Thus, the principal function of circulating IGFBP-3, in addition to the transport of IGFs, is the protection of the IGFs from rapid clearance and/or degradation [4]. At the cellular level, it has become clear that IGFBPs 1–6 have intrinsic biological activity (i.e., IGF/IGF-1R-independent actions) in addition to binding of IGFs, sequestering active hormones, and limiting IGF biological activity [5], [6]. These intrinsic cellular actions include proliferation, differentiation, migration, angiogenesis, and apoptosis in an IGF/IGF-1 receptor (IGF-1R)-independent manner [1], [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Protection of Blood Retinal Barrier and Systemic Vasculature by Insulin-Like Growth Factor Binding Protein-3

et al. 2012

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Previously, we showed that insulin growth factor (IGF)-1 binding protein-3 (IGFBP-3), independent of IGF-1, reduces pathological angiogenesis in a mouse model of the oxygen-induced retinopathy (OIR). The current study evaluates novel endothelium-dependent functions of IGFBP-3 including blood retinal barrier (BRB) integrity and vasorelaxation. To evaluate vascular barrier function, either plasmid expressing IGFBP-3 under the regulation of an endothelial-specific promoter or a control plasmid was injected into the vitreous humor of mouse pups (P1) and compared to the non-injected eyes of the same pups undergoing standard OIR protocol. Prior to sacrifice, the mice were given an injection of horseradish peroxidase (HRP). IGFBP-3 plasmid-injected eyes displayed near-normal vessel morphology and enhanced vascular barrier function. Further, in vitro IGFBP-3 protects retinal endothelial cells from VEGF-induced loss of junctional integrity by antagonizing the dissociation of the junctional complexes. To assess the vasodilatory effects of IGFBP-3, rat posterior cerebral arteries were examined in vitro. Intraluminal IGFBP-3 decreased both pressure- and serotonin-induced constrictions by stimulating nitric oxide (NO) release that were blocked by L-NAME or scavenger receptor-B1 neutralizing antibody (SRB1-Ab). Both wild-type and IGF-1-nonbinding mutant IGFBP-3 (IGFBP-3NB) stimulated eNOS activity/NO release to a similar extent in human microvascular endothelial cells (HMVECs). NO release was neither associated with an increase in intracellular calcium nor decreased by Ca2+/calmodulin-dependent protein kinase II (CamKII) blockade; however, dephosphorylation of eNOS-Thr495 was observed. Phosphatidylinositol 3-kinase (PI3K) activity and Akt-Ser473 phosphorylation were both increased by IGFBP-3 and selectively blocked by the SRB1-Ab or PI3K blocker LY294002. In conclusion, IGFBP-3 mediates protective effects on BRB integrity and mediates robust NO release to stimulate vasorelaxation via activation of SRB1. This response is IGF-1- and calcium-independent, but requires PI3K/Akt activation, suggesting that IGFBP-3 has novel protective effects on retinal and systemic vasculature and may be a therapeutic candidate for ocular complications such as diabetic retinopathy.

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“…Insulin-like growth factor binding protein 6 (IGFBP6) and glioblastoma amplified sequence (GBAS) are over-expressed in PAP-RCC. IGF binding proteins are biomarkers for several types of cancer [15]. GBAS is a likely target for tyrosine kinases that is co-amplified in some cancers with epidermal growth factor receptor (EGFR) [16].…”

Section: Section III Results and Discussionmentioning

confidence: 99%

Emerging translational bioinformatics: Knowledge-guided biomarker identification for cancer diagnostics

Phan

Yin-Goen

Young

et al. 2009

2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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Advances in high-throughput genomic and proteomic technology have led to a growing interest in cancer biomarkers. These biomarkers can potentially improve the accuracy of cancer subtype prediction and subsequently, the success of therapy. In this paper, we describe emerging technology for enabling translational bioinformatics by improving biomarker identification. Specifically, we present an application that uses prior knowledge to identify the most biologically relevant gene ranking algorithm. Identification of statistically and biologically relevant biomarkers from high-throughput data can be unreliable due to the nature of the data — e.g., high technical variability, small sample size, and high dimension size. Furthermore, due to the lack of available training samples, data-driven machine learning methods are often insufficient without the support of knowledge-based algorithms. As a case study, we apply these knowledge-driven methods to renal cancer data and identify genes that are potential biomarkers for cancer subtype classification.

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Promotion of Cancer Cell Migration

Abstract: In contrast, SP600125, a JNK MAPK inhibitor, had no effect on migration. Knockdown of p38 MAPK using short interfering RNA blocked IGFBP-6-induced migration of RD cells. These results indicate that p38 MAPK is involved in IGFBP-6-induced IGF-independent RD cell migration.

Cited by 60 publications

References 56 publications

Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

Loss of NAC1 Expression Is Associated with Defective Bony Patterning in the Murine Vertebral Axis

Protection of Blood Retinal Barrier and Systemic Vasculature by Insulin-Like Growth Factor Binding Protein-3

Emerging translational bioinformatics: Knowledge-guided biomarker identification for cancer diagnostics

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