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

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.

View full text Add to dashboard Cite

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.

show abstract

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.

View full text Add to dashboard Cite

show abstract

“…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

326

236

View full text Add to dashboard Cite

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.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

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

Contact Info

Product

Resources

About