Importance of Ets1 Proto-Oncogene for Breast Cancer Progression

Dittmer, J; Vetter, Marcus; Blumenthal, Susan; Lindemann, Ralph K.; Kölbl, H

doi:10.1055/s-2004-822758

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…The transcription factor Ets1 is a known effector of MAPK and an activator of MMP1 gene transcription. MAPK activates Ets1 by phosphorylating a conserved threonine‐38 residue (25). We examined Thr phosphorylation status of Ets1 in cells transduced with SphK1 or stimulated with TNF‐α.…”

Section: Resultsmentioning

confidence: 99%

Dihydrosphingosine 1‐phosphate stimulates MMP1 gene expression via activation of ERK1/2‐Ets1 pathway in human fibroblasts

Yamanaka

Pei

et al. 2005

FASEB j.

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Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation of important regulators of inter- and intracellular signaling, sphingosine-1 phosphate (S1P), and dihydrosphingosine 1-phosphate (dhS1P). In this study, we investigated the role of SphK1 in the regulation of expression of matrix metalloproteinase 1 (MMP1) in dermal fibroblasts, a key event in regulation of extra cellular matrix. We show that overexpression of SphK1 up-regulated MMP1 protein, MMP1 mRNA, and MMP1 promoter activity, and this action of SphK1 required activation of the ERK1/2-Ets1 and NF-kappaB pathways. Furthermore, experiments using SphK1 specific siRNA demonstrated that SphK1 is required for the TNF-alpha stimulation of MMP1. Additional data revealed a specific role of dhS1P, and not S1P, as a mediator of SphK1-dependent activation of ERK1/2 and up-regulation of MMP1. The stimulatory effect of dhS1P was sensitive to pertussis toxin, suggesting a possible involvement of a G-protein-coupled receptor. In contrast, S1P, but not dhS1P, stimulated the induction of COX-2, which demonstrated selective actions of these two closely related bioactive lipids. In conclusion, this study describes a novel mode of SphK1 signaling through generation of dhS1P with a key role in mediating transcriptional responses to TNF-alpha. This is the first report of selective function of dhS1P as compared with the better studied S1P.

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Section: Resultsmentioning

confidence: 99%

Dihydrosphingosine 1‐phosphate stimulates MMP1 gene expression via activation of ERK1/2‐Ets1 pathway in human fibroblasts

Yamanaka

Pei

et al. 2005

FASEB j.

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“…Ets1 is a proto‐oncogene that enhances invasiveness of carcinoma cells and endothelial cells and is predictive of poor prognosis . In breast cancer, Ets1 is overexpressed , is elevated in drug resistant cell lines , and regulates matrix metalloproteinases (MMPs) that are associated with an invasive phenotype . The E‐box in the cathepsin B promoter region is indispensable for promoter activity .…”

Section: Regulation Of Cathepsin Bmentioning

confidence: 99%

Cathepsin B: Multiple roles in cancer

Aggarwal

Sloane

2014

Proteomics Clinical Apps

315

236

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Proteases, including intracellular proteases, play roles at many different stages of malignant progression. Our focus here is cathepsin B, a lysosomal cysteine cathepsin. High levels of cathepsin B are found in a wide variety of human cancers, levels that often induce secretion and association of cathepsin B with the tumor cell membrane. In experimental models, such as transgenic models of murine pancreatic and mammary carcinomas, causal roles for cathepsin B have been demonstrated in initiation, growth/tumor cell proliferation, angiogenesis, invasion, and metastasis. Tumor growth in transgenic models is promoted by cathepsin B in tumor-associated cells, for example, tumor-associated macrophages, as well as in tumor cells. In transgenic models, the absence of cathepsin B has been associated with enhanced apoptosis, yet cathepsin B also has been shown to contribute to apoptosis. Cathepsin B is part of a proteolytic pathway identified in xenograft models of human glioma; targeting only cathepsin B in these tumors is less effective than targeting cathepsin B in combination with other proteases or protease receptors. Understanding the mechanisms responsible for increased expression of cathepsin B in tumors and association of cathepsin B with tumor cell membranes is needed to determine whether targeting cathepsin B could be of therapeutic benefit.

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“…Many other prioritized genes (e.g., AFAP1 , ANTXR1 , COL4A1 , COL8A2 , EFEMP1 , ETS1 , LTBP2 , PCSK5 , PTPN1 , and SEMA3E ) also play roles in cytoskeletal reorganization, extracellular matrix (ECM) assembly, and/or cell adhesion, especially through focal adhesions [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. It has been well established that ECM composition, cytoskeletal organization, and cell adhesion are critical to TM regulation of IOP homeostasis [ 13 , 14 , 15 , 49 , 85 , 86 , 87 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes

Youngblood

Parker

Cai

et al. 2021

IJMS

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Elevated intraocular pressure (IOP) is the only modifiable risk factor for primary open-angle glaucoma (POAG). Herein we sought to prioritize a set of previously identified IOP-associated genes using novel and previously published datasets. We identified several genes for future study, including several involved in cytoskeletal/extracellular matrix reorganization, cell adhesion, angiogenesis, and TGF-β signaling. Our differential correlation analysis of IOP-associated genes identified 295 pairs of 201 genes with differential correlation. Pathway analysis identified β-estradiol as the top upstream regulator of these genes with ESR1 mediating 25 interactions. Several genes (i.e., EFEMP1, FOXC1, and SPTBN1) regulated by β-estradiol/ESR1 were highly expressed in non-glaucomatous human trabecular meshwork (TM) or Schlemm’s canal (SC) cells and specifically expressed in TM/SC cell clusters defined by single-cell RNA-sequencing. We confirmed ESR1 gene and protein expression in human TM cells and TM/SC tissue with quantitative real-time PCR and immunofluorescence, respectively. 17β-estradiol was identified in bovine, porcine, and human aqueous humor (AH) using ELISA. In conclusion, we have identified estrogen receptor signaling as a key modulator of several IOP-associated genes. The expression of ESR1 and these IOP-associated genes in TM/SC tissue and the presence of 17β-estradiol in AH supports a role for estrogen signaling in IOP regulation.

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Importance of Ets1 Proto-Oncogene for Breast Cancer Progression

Cited by 8 publications

References 19 publications

Dihydrosphingosine 1‐phosphate stimulates MMP1 gene expression via activation of ERK1/2‐Ets1 pathway in human fibroblasts

Dihydrosphingosine 1‐phosphate stimulates MMP1 gene expression via activation of ERK1/2‐Ets1 pathway in human fibroblasts

Cathepsin B: Multiple roles in cancer

Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes

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