Secretion and dual regulation between epidermal growth factor and transforming growth factor-β1 in MDA-MB-231 cell line in 42-hour-long cultures

Martı́nez-Carpio, Pere A.; Mur, Cristina; Fernández-Montolí, Maria-Eulalia; Ramón, Josep; Rosel, Pilar; Navarro, Miguel

doi:10.1016/s0304-3835(99)00261-x

Cited by 24 publications

(20 citation statements)

References 14 publications

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“…In the 1990s, using a KB human epithelial cell line, the inhibition of EGF binding was temperature dependent and occurred immediately following UVA light exposure, and appeared to be due to a decrease in the number of EGFR. In KB cells, EGFR binding is followed by its rapid receptosomal internalization and degradation, as we found previously in the MDA-MB-231 cell line after EGF stimulation (4,5). Photoactivated psoralens also inhibited the internalization of EGF, but had no apparent effect on EGF metabolism.…”

Section: Resultssupporting

confidence: 74%

Cutaneous epidermal growth factor receptor system following ultraviolet irradiation: exploring the role of molecular mechanisms

Martínez-Carpio¹,

Trelles

2010

Photodermatology, Photoimmunology &Amp; Photomedicine

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Section: Resultssupporting

confidence: 74%

Cutaneous epidermal growth factor receptor system following ultraviolet irradiation: exploring the role of molecular mechanisms

Martínez-Carpio¹,

Trelles

2010

Photodermatology, Photoimmunology &Amp; Photomedicine

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“…S1), which have been shown to express TGF-β1 [50-52]. While previous studies have demonstrated that FN mRNA levels and protein expression are both upregulated in response to TGF-β1 [53-56], it is not clear whether this translates into increased assembly of FN fibrils, which require application of cellular contractile forces to soluble FN.…”

Section: Resultsmentioning

confidence: 99%

Fibronectin fibrils regulate TGF-β1-induced Epithelial-Mesenchymal Transition

et al. 2017

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Epithelial-Mesenchymal Transition (EMT) is a dynamic process through which epithelial cells transdifferentiate from an epithelial phenotype into a mesenchymal phenotype. Previous studies have also demonstrated that both mechanical signaling and soluble growth factor signaling facilitate this process. One possible point of integration for mechanical and growth factor signaling is the extracellular matrix. Here we investigate the role of the extracellular matrix (ECM) protein fibronectin (FN) in this process. We demonstrate that inhibition of FN fibrillogenesis blocks activation of the Transforming Growth Factor-Beta (TGF-β) signaling pathway via Smad2 signaling, decreases cell migration and ultimately leads to inhibition of EMT. Results show that soluble FN, FN fibrils, or increased contractile forces are insufficient to independently induce EMT. We further demonstrate that inhibition of latent TGF-β1 binding to FN fibrils via either a monoclonal blocking antibody against the growth factor binding domain of FN or through use of a FN deletion mutant that lacks the growth factor binding domains of FN blocks EMT progression, indicating a novel role for FN in EMT in which the assembly of FN fibrils serves to localize TGF-β1 signaling to drive EMT.

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“…Cell Invasion-The metastatic MDA-MB-231 breast cancer cells secrete active TGF-␤ (22,23) and are TGF-␤-responsive (24). The importance of autocrine TGF-␤ signaling in regulation of MDA-MB-231 cell invasiveness was assessed by Matrigel invasion assays following abrogation of autocrine TGF-␤ signaling using the LY364947 compound (27,28), a kinase inhibitor of TGF-␤ type I receptor (T␤RI) by functioning as a potent ATP competitive inhibitor.…”

Section: Autocrine Tgf-␤ Signaling Contributes To Mda-mb-231mentioning

confidence: 99%

“…Clinically, elevated uPA expression in tumors is associated with tumor aggressiveness and poor outcome in patients (16,17) and numerous studies have linked uPA to invasive and metastatic phenotype of tumors in vitro and in animal models (18 -21). The metastatic MDA-MB-231 breast cancer cells secrete active TGF-␤ (22,23) and are TGF-␤-responsive (24). These cells also express both the matrix metalloproteinases-9 (MMP-9) and uPA (20,25,26).…”

mentioning

confidence: 99%

Smad4-dependent Regulation of Urokinase Plasminogen Activator Secretion and RNA Stability Associated with Invasiveness by Autocrine and Paracrine Transforming Growth Factor-β

Shiou

Datta

Dhawan

et al. 2006

Journal of Biological Chemistry

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Metastasis is a primary cause of mortality due to cancer. Early metastatic growth involves both a remodeling of the extracellular matrix surrounding tumors and invasion of tumors across the basement membrane. Up-regulation of extracellular matrix degrading proteases such as urokinase plasminogen activator (uPA) and matrix metalloproteinases has been reported to facilitate tumor cell invasion. Autocrine transforming growth factor-␤ (TGF-␤) signaling may play an important role in cancer cell invasion and metastasis; however, the underlying mechanisms remain unclear. In the present study, we report that autocrine TGF-␤ supports cancer cell invasion by maintaining uPA levels through protein secretion. Interestingly, treatment of paracrine/exogenous TGF-␤ at higher concentrations than autocrine TGF-␤ further enhanced uPA expression and cell invasion. The enhanced uPA expression by exogenous TGF-␤ is a result of increased uPA mRNA expression due to RNA stabilization. We observed that both autocrine and paracrine TGF-␤-mediated regulation of uPA levels was lost upon depletion of Smad4 protein by RNA interference. Thus, through the Smad pathway, autocrine TGF-␤ maintains uPA expression through facilitated protein secretion, thereby supporting tumor cell invasiveness, whereas exogenous TGF-␤ further enhances uPA expression through mRNA stabilization leading to even greater invasiveness of the cancer cells.Malignant tumors are characterized by their ability to metastasize to distant organs. The initial steps of metastasis involve invasive growth of tumors across the basement membrane and migration through the extracellular matrix (ECM).2 Because the enzymatic degradation of both the basement membrane and ECM barriers requires a number of ECM-degrading proteases (1, 2) and is a critical early event in metastasis, invasiveness may be modulated by the expression of ECM-degrading proteases in tumor cells in response to autonomous and microenvironmental signals. Among the increasing number of ECMdegrading proteases implicated in metastasis, considerable attention has been focused on the family of matrix metalloproteinases (MMPs) and the plasminogen activator system. One of the regulators of these ECM-degrading proteases is transforming growth factor-␤ (TGF-␤).TGF-␤ is a multifunctional cytokine that regulates cell proliferation, differentiation, plasticity, and migration in a contextdependent manner (reviewed in Refs. 3 and 4). TGF-␤ transduces signaling through a transmembrane type II receptor (T␤RII), a constitutively active serine/threonine kinase receptor (5). Upon ligand binding, the T␤RII recruits and transphosphorylates intracellular TGF-␤ type I receptor (T␤RI), thereby stimulating T␤RI serine/threonine kinase activity (6). The T␤RI then activates the downstream effectors, Smad2 and Smad3, by phosphorylation. The activated Smad proteins form complexes with the common Smad mediator, Smad4, and then translocate to the nucleus, where the Smad complexes regulate transcription of TGF-␤ target genes in conjunction with vario...

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Secretion and dual regulation between epidermal growth factor and transforming growth factor-β1 in MDA-MB-231 cell line in 42-hour-long cultures

Cited by 24 publications

References 14 publications

Cutaneous epidermal growth factor receptor system following ultraviolet irradiation: exploring the role of molecular mechanisms

Cutaneous epidermal growth factor receptor system following ultraviolet irradiation: exploring the role of molecular mechanisms

Fibronectin fibrils regulate TGF-β1-induced Epithelial-Mesenchymal Transition

Smad4-dependent Regulation of Urokinase Plasminogen Activator Secretion and RNA Stability Associated with Invasiveness by Autocrine and Paracrine Transforming Growth Factor-β

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