Osteopontin Induces AP-1-mediated Secretion of Urokinase-type Plasminogen Activator through c-Src-dependent Epidermal Growth Factor Receptor Transactivation in Breast Cancer Cells

Das, Riku; Mahabeleshwar, Ganapati H.; Kundu, Gopal C.

doi:10.1074/jbc.m310256200

Cited by 101 publications

(73 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transfected or treated cells were further treated with OPN. The nuclear extracts were prepared as described earlier (37). Briefly the cells were resuspended in hypotonic buffer (10 mM Hepes (pH 7.9), 1.5 mM MgCl 2 , 10 mM KCl, 0.2 mM phenylmethylsulfonyl fluoride, and 0.5 mM dithiothreitol).…”

Section: Methodsmentioning

confidence: 99%

“…EMSA-To check whether NIK and IKK play any role in OPNinduced NF B-DNA binding, cells were either treated with 5 M OPN or transfected with wild type NIK, kinase-negative NIK, or wild type and dn IKK␤ and then treated with OPN for 6 h at 37°C, and EMSA was performed as described previously (37). To investigate whether MEK-1 or ERK1/2 is involved in OPN-induced NF B-DNA binding and whether it is regulated by NIK, cells were either pretreated with PD98059 or transfected with wt NIK or kinase-negative NIK and then treated with PD98059 or transfected with wild type and dn ERK1 and ERK2.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Nuclear Factor-inducing Kinase Plays a Crucial Role in Osteopontin-induced MAPK/IκBα Kinase-dependent Nuclear Factor κB-mediated Promatrix Metalloproteinase-9 Activation

Rangaswami

Bulbule

Kundu

2004

Journal of Biological Chemistry

Self Cite

164

142

View full text Add to dashboard Cite

We have recently demonstrated that osteopontin (OPN) induces nuclear factor B (NF B)-mediated promatrix metalloproteinase-2 activation through I B␣/ I B␣ kinase (IKK) signaling pathways. However, the molecular mechanism(s) by which OPN regulates promatrix metalloproteinase-9 (pro-MMP-9) activation, MMP-9-dependent cell motility, and tumor growth and the involvement of upstream kinases in regulation of these processes in murine melanoma cells are not well defined. Here we report that OPN induced ␣ v ␤ 3 integrinmediated phosphorylation and activation of nuclear factor-inducing kinase (NIK) and enhanced the interaction between phosphorylated NIK and IKK␣/␤ in B16F10 cells. Moreover, NIK was involved in OPN-induced phosphorylations of MEK-1 and ERK1/2 in these cells. OPN induced NIK-dependent NF B activation through ERK/ IKK␣/␤-mediated pathways. Furthermore OPN enhanced NIK-regulated urokinase-type plasminogen activator (uPA) secretion, uPA-dependent pro-MMP-9 activation, cell motility, and tumor growth. Wild type NIK, IKK␣/␤, and ERK1/2 enhanced and kinase-negative NIK (mut NIK), dominant negative IKK␣/␤ (dn IKK␣/␤), and dn ERK1/2 suppressed the OPN-induced NF B activation, uPA secretion, pro-MMP-9 activation, cell motility, and chemoinvasion. Pretreatment of cells with anti-MMP-2 antibody along with anti-MMP-9 antibody drastically inhibited the OPN-induced cell migration and chemoinvasion, whereas cells pretreated with anti-MMP-2 antibody had no effect on OPN-induced pro-MMP-9 activation suggesting that OPN induces pro-MMP-2 and pro-MMP-9 activations through two distinct pathways. The level of active MMP-9 in the OPN-induced tumor was higher compared with control. To our knowledge, this is the first report that NIK plays a crucial role in OPN-induced NF B activation, uPA secretion, and pro-MMP-9 activation through MAPK/IKK␣/␤-mediated pathways, and all of these ultimately control the cell motility, invasiveness, and tumor growth.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Nuclear Factor-inducing Kinase Plays a Crucial Role in Osteopontin-induced MAPK/IκBα Kinase-dependent Nuclear Factor κB-mediated Promatrix Metalloproteinase-9 Activation

Rangaswami

Bulbule

Kundu

2004

Journal of Biological Chemistry

Self Cite

164

142

View full text Add to dashboard Cite

show abstract

“…This pathway can also induce NIK-dependent NFκβ activation through IKK/ERK mediated pathways stimulating uPA-dependent MMP9 activation [9]. A further signaling cascade involves the stimulation of c-Src dependent epidermal growth factor receptor (EGFR) transactivation and activation of FAK, paxillin and vinculin which regulate cell attachment and migration [10,34].…”

Section: Introductionmentioning

confidence: 99%

Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

et al. 2007

View full text Add to dashboard Cite

Osteopontin (OPN) is a pleotrophic molecule that has been associated with multiple disorders of the central nervous system (CNS). Its roles in CNS malignancy are unclear but suggest that higher levels of OPN expression correlate with increased tumor grade and increased migratory capacity of tumor cells. In this study OPN cDNA was cloned into a retroviral vector and used to infect F98 Fischer rat-derived glioma cells and U87 human-derived glioblastoma multiforme (GBM) cells in vitro. Cells expressing high levels of OPN migrated less distance than control cells in vitro. This

show abstract

“…transcription via NFjB and AP-1 (Das et al, 2004(Das et al, , 2005Philip and Kundu, 2003;Rangaswami et al, 2005). Binding of Opn to its receptors induces PI3K ⁄ Akt-dependent NFjB activation and uPA secretion in cancer cells (Das et al, 2005).…”

Section: Alcohol-induced Fibrogenesis Modulated Via Plasmin-plasminogmentioning

confidence: 99%

“…Binding of Opn to its receptors induces PI3K ⁄ Akt-dependent NFjB activation and uPA secretion in cancer cells (Das et al, 2005). uPA ⁄ tPA, MMP9, and plasmin are also activated via MAPK and Erk pathways activating transcription factors AP-1 in breast and prostate cancer cells (Angelucci et al, 2002;Das et al, 2004;Philip and Kundu, 2003). Intriguingly, findings in human ALD show for the first time a significant increase in expression of Opn, Opn receptors (integrins, CD44), Opn modifiers (thrombin, MMPs, tissue inhibitors of MMP [TIMPs]) and downstream effectors (uPA, tPA, plasminogen) (Seth et al, 2003(Seth et al, , 2006a.…”

Section: Alcohol-induced Fibrogenesis Modulated Via Plasmin-plasminogmentioning

confidence: 99%

Alcohol, Signaling, and ECM Turnover

Seth

El-Guindy

Apte

et al. 2009

Alcoholism Clin & Exp Res

Self Cite

View full text Add to dashboard Cite

Alcohol is recognized as a direct hepatotoxin, but the precise molecular pathways that are important for the initiation and progression of alcohol-induced tissue injury are not completely understood. The current understanding of alcohol toxicity to organs suggests that alcohol initiates injury by generation of oxidative and nonoxidative ethanol metabolites and via translocation of gut-derived endotoxin. These processes lead to cellular injury and stimulation of the inflammatory responses mediated through a variety of molecules. With continuing alcohol abuse, the injury progresses through impairment of tissue regeneration and extracellular matrix (ECM) turnover, leading to fibrogenesis and cirrhosis. Several cell types are involved in this process, the predominant being stellate cells, macrophages, and parenchymal cells. In response to alcohol, growth factors and cytokines activate many signaling cascades that regulate fibrogenesis. This mini-review brings together research focusing on the underlying mechanisms of alcohol-mediated injury in a number of organs. It highlights the various processes and molecules that are likely involved in inflammation, immune modulation, susceptibility to infection, ECM turnover and fibrogenesis in the liver, pancreas, and lung triggered by alcohol abuse.

show abstract

Osteopontin Induces AP-1-mediated Secretion of Urokinase-type Plasminogen Activator through c-Src-dependent Epidermal Growth Factor Receptor Transactivation in Breast Cancer Cells

Cited by 101 publications

References 53 publications

Nuclear Factor-inducing Kinase Plays a Crucial Role in Osteopontin-induced MAPK/IκBα Kinase-dependent Nuclear Factor κB-mediated Promatrix Metalloproteinase-9 Activation

Nuclear Factor-inducing Kinase Plays a Crucial Role in Osteopontin-induced MAPK/IκBα Kinase-dependent Nuclear Factor κB-mediated Promatrix Metalloproteinase-9 Activation

Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal

Alcohol, Signaling, and ECM Turnover

Contact Info

Product

Resources

About