Growth Inhibition by Insulin-like Growth Factor-binding Protein-3 in T47D Breast Cancer Cells Requires Transforming Growth Factor-β (TGF-β) and the Type II TGF-β Receptor

Fanayan, Susan; Firth, Sue M.; Butt, Alison J.; Baxter, Robert C.

doi:10.1074/jbc.m006964200

Cited by 111 publications

(95 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most interestingly, these studies suggest that the T␤RI is not responsible for the EGF-induced Smad phosphorylation, since it is evident in R1B cells, which lack the type I receptor. Additionally, IGFBP-3 is a further biological mediator, which is capable to stimulate Smad2 and Smad3 phosphorylation and moreover to potentiate TGF-␤-induced Smad activation (21,23). However, in contrast to the EGF-induced Smad activation, these studies indicate that IGFBP-3 signaling in T47D and MCF-7 breast cancer cells activates T␤RI and that this requires the presence of T␤RII.…”

Section: Figmentioning

confidence: 88%

“…Thus, it has been reported that the insulin-like growth factor binding protein-3 (IGFBP-3) can stimulate Smad2 and Smad3 phosphorylation. Although this activation occurs in the absence of endogenous or exogenous TGF-␤, it requires the T␤RII, implying an interaction between IGFBP receptors and TGF-␤ receptors (21)(22)(23). S1P receptors are also known to cross-communicate with other GPCRs as well as other plasma membrane receptors, including receptor-tyrosine kinases (24 -26).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Involvement of Smad Signaling in Sphingosine 1-Phosphate-mediated Biological Responses of Keratinocytes

Sauer

Vogler

Wenckstern

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The lysophospholipid sphingosine 1-phosphate and the cytokine-transforming growth factor ␤ are both released from degranulating platelets at wound sites, suggesting a broad spectrum of effects involved in wound healing. Interestingly, both of these molecules have been previously shown to induce chemotaxis but to strongly inhibit the growth of keratinocytes, while stimulating the proliferation of fibroblasts. In contrast to sphingosine 1-phosphate, the signaling cascade of the growth factor has been extensively examined. Specifically, Smad3 has been shown to be an essential mediator of transforming growth factor ␤-dependent chemotaxis of keratinocytes and mediates, in part, its growth-inhibitory effect. Here we show that sphingosine 1-phosphate, independently of transforming growth factor ␤ secretion, induces a rapid phosphorylation of Smad3 on its C-terminal serine motif and induces its partnering with Smad4 and the translocation of the complex into the nucleus. Moreover, sphingosine 1-phosphate fails to induce chemotaxis or inhibit the growth of Smad3-deficient keratinocytes, suggesting that Smad3 plays an unexpected functional role as a new target in sphingosine 1-phosphate signaling. Both sphingosine 1-phosphate receptors and the transforming growth factor ␤-type I receptor serine/threonine kinase are essential for activation of Smad3 by this lysophospholipid and the dependent biological responses, indicating a novel crosstalk between serine/threonine kinase receptors and G-protein coupled receptors.

show abstract

Section: Figmentioning

confidence: 88%

mentioning

confidence: 99%

Involvement of Smad Signaling in Sphingosine 1-Phosphate-mediated Biological Responses of Keratinocytes

Sauer

Vogler

Wenckstern

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In cells transfected to express TGF-␤ receptor type II, insulin-like growth factor binding protein-3 (IGFBP-3) stimulated Smad2 and Smad3 phosphorylation, potentiated TGF-␤1-stimulated Smad phosphorylation, and cooperated with exogenous TGF-␤1 in cell growth inhibition. 30 In PC12 cells, nerve growth factor led to activation of the Smad pathway independent of TGF-␤. 31 Advanced glycation end products caused rapid Smad2/3 activation in renal and vascular cells that was independent of TGF-␤, 32 suggesting the importance of Smad pathway in diabetic organ injury.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Activates the Smad Pathway in Vascular Smooth Muscle Cells by a Transforming Growth Factor-β–Independent Mechanism

Rodríguez-Vita¹,

Sánchez-López²,

Esteban³

et al. 2005

Circulation

301

267

View full text Add to dashboard Cite

Background— Angiotensin II (Ang II) participates in vascular fibrosis. Transforming growth factor-β (TGF-β) is considered the most important fibrotic factor, and Smad proteins are essential components of the TGF-β signaling system. Our aim was to investigate whether Ang II activates the Smad pathway in vascular cells and its potential role in fibrosis, evaluating connective tissue growth factor (CTGF) and extracellular matrix (ECM) proteins. Methods and Results— Systemic infusion of Ang II into Wistar rats increased aortic Smad2, phosphorylated-Smad2, and Smad4 expression, associated with CTGF upregulation. In growth-arrested vascular smooth muscle cells, Ang II treatment for 20 minutes caused Smad2 phosphorylation, nuclear translocation of phosphorylated-Smad2 and Smad4, and increased Smad DNA-binding activity. Ang II also caused Smad overexpression and Smad-dependent gene transcription. The AT 1 antagonist losartan diminished Ang II-induced Smad activation. The blockade of endogenous TGF-β did not modify the activation of Smad caused by Ang II. The p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 diminished Ang II-induced Smad2 phosphorylation. These data show that Ang II activates the Smad pathway via AT 1 receptors and MAPK activation independently of TGF-β. Transient transfection with Smad7, which interferes with receptor-mediated activation of Smad2, diminished Ang II-induced CTGF promoter activation, gene and protein expression, and fibronectin and type-1 procollagen overexpression, showing that Smad activation is involved in Ang II-induced fibrosis. Conclusions— Our results show that Ang II activates the Smad signaling system in vascular cells in vivo and in vitro. Smad proteins are involved in Ang II-induced CTGF and ECM overexpression independently of TGF-β. This novel finding suggests that Smad activation could be involved in the profibrogenic effects of Ang II in vascular diseases.

show abstract

“…In T47D breast cancer cells, that lack TβRII, restoration of this receptor by transfection sensitized the cells to Smad2 and Smad3 phosphorylation, and inhibition of cell proliferation, by IGFBP-3 (Fanayan, et al 2000). TβRI was also phosphorylated in response to IGFBP-3, suggesting that IGFBP-3 required an intact TGFβ signaling pathway for growth inhibition of this cell line (Fanayan, et al 2002).…”

Section: Lrp1 and Tgfβ Signalingmentioning

confidence: 95%

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions

Baxter

2013

J. Cell Commun. Signal.

Self Cite

View full text Add to dashboard Cite

In addition to its important role in the regulation of somatic growth by acting as the major circulating transport protein for the insulin-like growth factors (IGFs), IGF binding protein-3 (IGFBP-3) has a variety of intracellular ligands that point to its function within major signaling pathways. The discovery of its interaction with the retinoid X receptor has led to the elucidation of roles in regulating the function of several nuclear hormone receptors including retinoic acid receptor-α, Nur77 and vitamin D receptor. Its interaction with the nuclear hormone receptor peroxisome proliferator-activated receptor-γ is believed to be involved in regulating adipocyte differentiation, which is also modulated by IGFBP-3 through an interaction with TGFβ/Smad signaling. IGFBP-3 can induce apoptosis alone or in conjunction with other agents, and in different systems can activate caspases −8 and −9. At least two unrelated proteins (LRP1 and TMEM219) have been designated as receptors for IGFBP-3, the latter with a demonstrated role in inducing caspase-8-dependent apoptosis. In contrast, IGFBP-3 also has demonstrated roles in survival-related functions, including the repair of DNA double-strand breaks through interaction with the epidermal growth factor receptor and DNAdependent protein kinase, and the induction of autophagy through interaction with GRP78. The ability of IGFBP-3 to modulate the balance between pro-apoptotic and prosurvival sphingolipids by regulating sphingosine kinase 1 and sphingomyelinases may be integral to its role at the crossroads between cell death and survival in response to a variety of stimuli. The pleiotropic nature of IGFBP-3 activity supports the idea that IGFBP-3 itself, or pathways with which it interacts, should be investigated as targets of therapy for a variety of diseases.

show abstract

Growth Inhibition by Insulin-like Growth Factor-binding Protein-3 in T47D Breast Cancer Cells Requires Transforming Growth Factor-β (TGF-β) and the Type II TGF-β Receptor

Cited by 111 publications

References 56 publications

Involvement of Smad Signaling in Sphingosine 1-Phosphate-mediated Biological Responses of Keratinocytes

Involvement of Smad Signaling in Sphingosine 1-Phosphate-mediated Biological Responses of Keratinocytes

Angiotensin II Activates the Smad Pathway in Vascular Smooth Muscle Cells by a Transforming Growth Factor-β–Independent Mechanism

Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions

Contact Info

Product

Resources

About