scholarly journals Insulin-Like Growth Factor Binding Protein-3 Induces Insulin Resistance in Adipocytes In Vitro and in Rats In Vivo

2007 ◽  
Vol 61 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Hae Soon Kim ◽  
Omar Ali ◽  
Melanie Shim ◽  
Kuk-Wha Lee ◽  
Patricia Vuguin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding

scholarly journals Insulin-Like Growth Factor Binding Protein-3 Exerts Its Anti-Metastatic Effect in Aerodigestive Tract Cancers by Disrupting the Protein Stability of Vimentin

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1041
Author(s):  
Huong Thuy Le ◽  
Ho Jin Lee ◽  
Jaebeom Cho ◽  
Hye-Young Min ◽  
Ji-Sun Lee ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Stability ◽  
Binding Protein ◽  
Migration And Invasion ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Local Invasion ◽  
Igfbp 3

The proapoptotic, antiangiogenic, and antimetastatic activities of insulin-like growth factor binding protein-3 (IGFBP-3) through IGF-dependent or -independent mechanisms have been suggested in various types of human cancers. However, a mechanistic explanation of and downstream targets involved in the antimetastatic effect of IGFBP-3 is still lacking. In this study, by applying various in vitro and in vivo models, we show that IGFBP-3 suppresses migration and invasion of human head and neck squamous carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cells. Silencing IGFBP-3 expression elevated the migration and invasion of NSCLC and HNSCC cells in vitro and their local invasion and metastasis in vivo, whereas overexpression of IGFBP-3 decreased such prometastatic changes. Local invasion of 4-nitroquinoline-1-oxide (4-NQO)-induced HNSCC tumors was consistently significantly potentiated in Igfbp3 knockout mice compared with that in wild-type mice. Mechanistically, IGFBP-3 disrupted the protein stability of vimentin via direct binding and promoting its association with the E3 ligase FBXL14, causing proteasomal degradation. The C-terminal domain of IGFBP-3 and the head domain of vimentin are essential for their interaction. These results provide a molecular framework for IGFBP-3′s IGF-independent antimetastatic and antitumor activities.

scholarly journals Insulin-Like-Growth-Factor-Binding-Protein-3 (IGFBP-3) Contrasts Melanoma Progression In Vitro and In Vivo

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e98641 ◽  
Author(s):  
Antimo Naspi ◽  
Vincenzo Panasiti ◽  
Franco Abbate ◽  
Vincenzo Roberti ◽  
Valeria Devirgiliis ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Melanoma Progression ◽  
Igfbp 3

scholarly journals Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

1999 ◽  
Vol 161 (3) ◽  
pp. 465-474 ◽  
Author(s):  
I Demori ◽  
C Bottazzi ◽  
E Fugassa
Keyword(s):  
Growth Factor ◽  
Thyroid Hormone ◽  
Binding Protein ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Insulin Like Growth Factor ◽  
Cultured Hepatocytes ◽  
Factor Binding

Previous evidence suggests the existence of a thyroid hormone-IGF axis in the liver and changes in hepatic insulin-like growth factor binding protein (IGFBP) expression in rats with altered thyroid status have been previously reported. The aim of this study was to check if the higher IGFBP-2 mRNA levels observed in liver of hypothyroid rats could be due to a direct effect of thyroid hormone on the IGFBP-2 gene. In our experiments, cultured hepatocytes isolated from normal and hypothyroid adult rats were used. Northern blot analysis revealed barely detectable IGFBP-2 mRNA in normal rat hepatocytes, but easily detectable signal in hypothyroid rat cells. Therefore, the effect of tri-iodothyronine (T3) was investigated using cultured hepatocytes from hypothyroid rats as an in vitro model. The IGFBP-2 message was increased in a dose-dependent manner in hepatocytes cultured for 12-24 h in the presence of T3. A similar increase occurred in accumulation of IGFBP-2 in the culture medium, as measured by RIA. The effect of T3 on IGFBP-2 transcript levels appeared to consist of enhanced gene transcription and was independent of ongoing protein synthesis, but it was completely abolished by the incubation of hepatocytes with insulin. The latter result confirmed the dominant role of insulin in regulating IGFBP-2 expression by cultured hepatocytes. In vivo experiments confirmed an increase in hepatic IGFBP-2 mRNA and serum IGFBP-2 levels in hypothyroid rats and demonstrated, in addition, a significant increase in these measures in T3-treated rats. Taken together, our in vitro and in vivo results support a role for a thyroid hormone-IGF axis in the liver and suggest that other factors, such as insulin, interact in vivo with thryoid hormone in regulating hepatic IGFBP-2 expression.

scholarly journals EWS/FLI-1 Silencing and Gene Profiling of Ewing Cells Reveal Downstream Oncogenic Pathways and a Crucial Role for Repression of Insulin-Like Growth Factor Binding Protein 3

2004 ◽  
Vol 24 (16) ◽  
pp. 7275-7283 ◽  
Author(s):  
Alexandre Prieur ◽  
Franck Tirode ◽  
Pinchas Cohen ◽  
Olivier Delattre
Keyword(s):  
Growth Factor ◽  
Fusion Gene ◽  
Binding Protein ◽  
Gene Profiling ◽  
Insulin Like Growth Factor ◽  
Small Interfering Rnas ◽  
Factor Binding ◽  
Igfbp 3

ABSTRACT Ewing tumors are characterized by abnormal transcription factors resulting from the oncogenic fusion of EWS with members of the ETS family, most commonly FLI-1. RNA interference targeted to the junction between EWS and FLI-1 sequences was used to inactivate the EWS/FLI-1 fusion gene in Ewing cells and to explore the resulting phenotype and alteration of the gene expression profile. Loss of expression of EWS/FLI-1 resulted in the complete arrest of growth and was associated with a dramatic increase in the number of apoptotic cells. Gene profiling of Ewing cells in which the EWS/FLI-1 fusion gene had been inactivated identified downstream targets which could be grouped in two major functional clusters related to extracellular matrix structure or remodeling and regulation of signal transduction pathways. Among these targets, the insulin-like growth factor binding protein 3 gene (IGFBP-3), a major regulator of insulin-like growth factor 1 (IGF-1) proliferation and survival signaling, was strongly induced upon treating Ewing cells with EWS/FLI-1-specific small interfering RNAs. We show that EWS/FLI-1 can bind the IGFBP-3 promoter in vitro and in vivo and can repress its activity. Moreover, IGFBP-3 silencing can partially rescue the apoptotic phenotype caused by EWS/FLI-1 inactivation. Finally, IGFBP-3-induced Ewing cell apoptosis relies on both IGF-1-dependent and -independent pathways. These findings therefore identify the repression of IGFBP-3 as a key event in the development of Ewing's sarcoma.

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