Transforming growth factor beta 1 and sodium butyrate differentially modulate urokinase plasminogen activator and plasminogen activator inhibitor-1 in human breast normal and cancer cells

Bourhis, Xuefen Dong-Le; Lambrecht, V; Boilly, B

doi:10.1038/bjc.1998.63

Cited by 20 publications

(4 citation statements)

References 27 publications

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“…As shown previously,28 linoleic acid had the greatest effect on the induction of PAI-1 in MDA-MB-231 cells, consistent with our previous observations that linoleic acid increased the expression of PAI-1 in HepG2 cells 18,19. It was also reported that butyric acid inhibited both cell proliferation and uPA activity, but had no effect on PAI-1 level in MDA-MB-231 cells,29 again suggesting that FFAs with different saturation and chain lengths show different effects on the expression of PAI-1. A concentration of 500 μ M was selected for individual FFAs because our previous studies demonstrated that this concentration of FFAs induces PAI-1 expression in HepG2 cells 18,19.…”

Section: Discussionsupporting

confidence: 90%

“…TGF- β 1-induced PAI-1 has been reported to be associated with its stimulatory effect on invasion and metastasis of MDA-MB-231 cells 29. Incubation of endothelial cells with conditioned medium from two breast cancer cell lines (MCF7 and MDA-MB-231) also demonstrated that conditioned medium from highly invasive MDA-MB-231 cells increased the tube formation of endothelial cells, which was related to the high levels of uPA and PAI-1 secreted by MDA-MB-231 cells as compared with low levels in MCF7 cells 33.…”

Section: Discussionmentioning

confidence: 99%

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Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4

Byon

Hardy

Ren

et al. 2009

Laboratory Investigation

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Obesity is a risk factor for breast cancer and is associated with increased plasma concentrations of free fatty acids (FFAs). We and others have demonstrated that FFA induces plasminogen activator inhibitor-1 (PAI-1) expression in a variety of cells. Emerging evidence supports elevation of PAI-1 as a prognostic marker for breast cancer. Therefore, we hypothesized that FFAs might increase expression of PAI-1 in breast cancer cells and facilitate breast cancer progression. Secreted PAI-1 was higher in invasive and metastatic MDA-MB-231 cells compared with less invasive and non-metastatic Hs578T cells. Utilizing FFAs with different saturation and chain lengths, we demonstrated that linoleic acid induced expression of PAI-1 in MDA-MB-231 cells. Linoleic acid also induced in vitro migration of MDA-MB-231. By contrast, other FFAs tested had little or no effect on PAI-1 expression or migration. Linoleic acid-induced breast cancer cell migration was completely inhibited by virally expressed antisense PAI-1 RNA. Furthermore, increased expression of PAI-1 by FFAs was not detected in the SMAD4-deficient MDA-MB-468 breast carcinoma cells. Electrophoretic mobility-shift assay confirmed that linoleic acid-induced expression of PAI-1 was mediated, at least in part, by SMAD4 in MDA-MB-231 cells. That linoleic acid induces PAI-1 expression in breast cancer cells through SMAD4 provides a novel insight into understanding the relationships between two migration-associated molecules, FFAs, and PAI-1.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4

Byon

Hardy

Ren

et al. 2009

Laboratory Investigation

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“…PAI1 and IGFBP-3 are also associated to the TGF-beta receptor signaling pathway [102], an interaction which was indicated in our HS578T/NOD2 protein network (Fig 3. b), as well as their downstream signaling to the major interacting node ERK1/2, (Fig.…”

Section: Discussionmentioning

confidence: 70%

“…As PLAU inhibitor, PAI1 is directly involved in extracellular matrix remodeling and cell adhesion [115], promoting tumor progression and metastasis in several cancers, including breast cancer [116]. Interestingly, the effects of PAI1 in breast tumor progression seems to be regulated by a non-canonical TGF-beta1 pathway [102, 117, 118]. Moreover, it has also been proposed that PAI1 may regulate cell migration independently of its role as protease inhibitor [119, 120].…”

Section: Discussionmentioning

confidence: 99%

Proteome profiling of triple negative breast cancer cells overexpressing NOD1 and NOD2 receptors unveils molecular signatures of malignant cell proliferation

et al. 2019

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Background Triple negative breast cancer (TNBC) is a malignancy with very poor prognosis, due to its aggressive clinical characteristics and lack of response to receptor-targeted drug therapy. In TNBC, immune-related pathways are typically upregulated and may be associated with a better prognosis of the disease, encouraging the pursuit for immunotherapeutic options. A number of immune-related molecules have already been associated to the onset and progression of breast cancer, including NOD1 and NOD2, innate immune receptors of bacterial-derived components which activate pro-inflammatory and survival pathways. In the context of TNBC, overexpression of either NOD1 or NOD2 is shown to reduce cell proliferation and increase clonogenic potential in vitro. To further investigate the pathways linking NOD1 and NOD2 signaling to tumorigenesis in TNBC, we undertook a global proteome profiling of TNBC-derived cells ectopically expressing each one of these NOD receptors. Results We have identified a total of 95 and 58 differentially regulated proteins in NOD1 - and NOD2 -overexpressing cells, respectively. We used bioinformatics analyses to identify enriched molecular signatures aiming to integrate the differentially regulated proteins into functional networks. These analyses suggest that overexpression of both NOD1 and NOD2 may disrupt immune-related pathways, particularly NF-κB and MAPK signaling cascades. Moreover, overexpression of either of these receptors may affect several stress response and protein degradation systems, such as autophagy and the ubiquitin-proteasome complex. Interestingly, the levels of several proteins associated to cellular adhesion and migration were also affected in these NOD-overexpressing cells. Conclusions Our proteomic analyses shed new light on the molecular pathways that may be modulating tumorigenesis via NOD1 and NOD2 signaling in TNBC. Up- and downregulation of several proteins associated to inflammation and stress response pathways may promote activation of protein degradation systems, as well as modulate cell-cycle and cellular adhesion proteins. Altogether, these signals seem to be modulating cellular proliferation and migration via NF-κB, PI3K/Akt/mTOR and MAPK signaling pathways. Further investigation of altered proteins in these pathways may provide more insights on relevant targets, possibly enabling the immunomodulation of tumorigenesis in the aggressive TNBC phenotype. Electronic supplementary material The online version of this article (10.1186/s12864-019-5523-6) contains supplementary material, which is available to authorized users.

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Regulation of urokinase plasminogen activator (uPA) activity by E-cadherin and hormones in mammary epithelial cells

1999

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Urokinase plasminogen activator (uPA) is involved in proteolysis of extracellular matrix during development and tumor cell invasion. In the present study, we examined the regulation of uPA in hormone-responsive, noninvasive mammary epithelial cells by using fibrinolytic and caseinolytic enzyme activity assays. Urokinase PA expression was activated after contact with fibrin and initiation of cell-cell interactions that were mediated by E-cadherin. Fibrinolysis occurred in zones surrounding cellular aggregates. Stromal matrix proteins that disrupted aggregation or anti-E-cadherin antibodies that inhibited cellular compaction inhibited fibrinolysis perhaps by increasing cell-matrix adhesion or preventing E-cadherin signaling, respectively. Aggregation required the presence of divalent cations and was inhibited by serum and ethylene diaminetetraacetic acid, whereas serine protease inhibitors reduced uPA activity without affecting aggregation. Inhibitors of PA (type 2; PAI-2) and a specific antisense uPA oligonucleotide also reduced enzymatic activity, suggesting that fibrinolysis depends on translational regulation of uPA. In addition, the activation of plasmin from plasminogen was inhibited by anti-E-cadherin antibodies and PAI-2, consistent with a role for uPA. The data also support a role for transcriptional regulation of uPA activity because treatment of cells with progesterone, hydrocortisone, or dexamethasone inhibited uPA activation on fibrin without affecting cellular aggregation. Estradiol and insulin did not alter, whereas human chorionic gonadotropin and prolactin increased uPA activity. The expression of the 55-kDa uPA activity was consistent with specific hormone action and correlated with protein expression by immunoblotting. Therefore, the alteration of downstream signaling events by hormones may affect uPA production. These results indicate that uPA is an enzyme that may be important in the degradation of extracellular matrix during development and that specific E-cadherin interactions and hormones can regulate its activity. Investigation of the regulation of uPA in these cells may be useful in understanding and manipulating mammary gland remodeling. J. Cell. Physiol. 181:1-13, 1999. Published 1999 Wiley-Liss, Inc.

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Transforming growth factor beta 1 and sodium butyrate differentially modulate urokinase plasminogen activator and plasminogen activator inhibitor-1 in human breast normal and cancer cells

Cited by 20 publications

References 27 publications

Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4

Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4

Proteome profiling of triple negative breast cancer cells overexpressing NOD1 and NOD2 receptors unveils molecular signatures of malignant cell proliferation

Regulation of urokinase plasminogen activator (uPA) activity by E-cadherin and hormones in mammary epithelial cells

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