Shedding of epithin/PRSS14 is induced by TGF-β and mediated by tumor necrosis factor-α converting enzyme

Lee, Hyo Seon; Park, Bo Mi; Cho, Youngkyung; Kim, Sauryang; Kim, Chungho; Kim, Moon Gyo; Park, Dongeun

doi:10.1016/j.bbrc.2014.09.055

Cited by 12 publications

(18 citation statements)

References 32 publications

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“…Since ST14/Prss14 is able to shed into the media [7, 11–14, 54], it may therefore have function in trans. Therefore, ST14/Prss14 expression can be also contributed from a cancer microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…Protease activity of ST14/Prss14 requires cleavage at Arg 614, presumably by autocatalysis (reviewed in [8–10]). Upon TGFβ induction, the ectodomain is further processed by the TNFα converting enzyme (ADAM17) to be shed from the membrane [11]. Phorbol ester can also induce shedding by regulating ST14/Prss14 binding to filamin, a cytoplasmic actin binding protein [12].…”

Section: Introductionmentioning

confidence: 99%

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Impact of suppression of tumorigenicity 14 (ST14)/serine protease 14 (Prss14) expression analysis on the prognosis and management of estrogen receptor negative breast cancer

et al. 2016

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To elucidate the role of a type II transmembrane serine protease, ST14/Prss14, during breast cancer progression, we utilized publically accessible databases including TCGA, GEO, NCI-60, and CCLE. Survival of breast cancer patients with high ST14/Prss14 expression is significantly poor in estrogen receptor (ER) negative populations regardless of the ratios of ST14/Prss14 to its inhibitors, SPINT1 or SPINT2. In a clustering of 1085 selected EMT signature genes, ST14/Prss14 is located in the same cluster with CDH3, and closer to post-EMT markers, CDH2, VIM, and FN1 than to the pre-EMT marker, CDH1. Coexpression analyses of known ST14/Prss14 substrates and transcription factors revealed context dependent action. In cell lines, paradoxically, ST14/Prss14 expression is higher in the ER positive group and located closer to CDH1 in clustering. This apparent contradiction is not likely due to ST14/Prss14 expression in a cancer microenvironment, nor due to negative regulation by ER. Genes consistently coexpressed with ST14/Prss14 include transcription factors, ELF5, GRHL1, VGLL1, suggesting currently unknown mechanisms for regulation. Here, we report that ST14/Prss14 is an emerging therapeutic target for breast cancer where HER2 is not applicable. In addition we suggest that careful conclusions should be drawn not exclusively from the cell line studies for target development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of suppression of tumorigenicity 14 (ST14)/serine protease 14 (Prss14) expression analysis on the prognosis and management of estrogen receptor negative breast cancer

et al. 2016

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“…On the other hand, it has also been shown that in renal fibrosis the reduction of Ecadherin is in part explained by TGF- induced proteolysis [4]. In the same way, TGF-1 signalling has been associated with the activation of metalloproteinases such as tumor necrosis factor-alpha converting enzyme (TACE) and the subsequent shedding process of transmembrane proteins [60,61].…”

Section: Introductionmentioning

confidence: 99%

The down regulation of megalin/LRP2 by transforming growth factor beta (TGF-β1) is mediated by the SMAD2/3 signalling pathway

Cabezas¹,

Farfán²,

Marzolo³

2019

Preprint

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Megalin/LRP2 is a receptor that plays important roles in the physiology of several organs, such as kidney, lung, intestine, and gallbladder; and also in the physiology of the nervous system. Megalin expression is reduced in diseases associated with fibrosis, including diabetic nephropathy, hepatic fibrosis and cholelithiasis, as well as in some breast and prostate cancers. One of the hallmarks of these conditions is the presence of the cytokine transforming growth factor beta (TGF-ß). Although TGF-ß has been implicated in the reduction of megalin levels, the molecular mechanism underlying this regulation is not well understood. Here, we show that treatment of two epithelial cell lines (from kidney and gallbladder) with TGF-ß1 is associated with decreased megalin mRNA and protein levels, and that these effects are reversed by inhibiting the TGF-ß1 type I receptor (TGF-ßRI).Based on in silico analyses, the two SMAD-binding elements (SBEs) in the megalin promoter are located at positions -57 and -605. Site-directed mutagenesis of the SBEs and chromatin immunoprecipitation (ChIP) experiments revealed that SMAD2/3 transcription factors interact with SBEs to repress the megalin promoter and that they are also required for the repressing role of TGF-ß1. In addition, high concentration of albumin reduced megalin expression and promoter activation that depend on the expression of SMAD2/3. Interestingly, the histone deacetylase inhibitor Trichostatin A (TSA), which induces megalin expression, reduced the effects of TGF-ß1on megalin mRNA levels. These data show the significance of TGF-ß and the SMAD2/3 signalling pathway in the regulation of megalin and explain the decreased megalin levels observed under conditions in which TGFß is upregulated, including fibrosis-associated diseases and cancer.

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“…lipid rafts), and their cytoplasmic extensions are frequently associated with membrane trafficking and/or signal transduction. In some situations, and frequently in response to inflammatory stimuli, the extracellular domains of membrane-anchored proteases are shed from the cell surface [47,49,53], which may indicate a down-regulation of the proteolytic functions of these enzymes. In addition, other mechanisms for regulation of cell surface protease activities exist, including natural inhibitors such as Kunitz-type inhibitors and serpins for the serine proteases and TIMPs for the metalloproteases, and protease endocytosis and turnover [47,54].…”

Section: Membrane Anchoring Domainsmentioning

confidence: 99%

Membrane-anchored proteases in endothelial cell biology

Antalis

Conway

Peroutka

et al. 2016

Current Opinion in Hematology

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Purpose of review The endothelial cell plasma membrane is a metabolically active, dynamic and fluid microenvironment where pericellular proteolysis plays a critical role. Membrane-anchored proteases may be expressed by endothelial cells, as well as mural cells and leukocytes with distribution both inside and outside of the vascular system. Here we will review the recent advances in our understanding of the direct and indirect roles of membrane-anchored proteases in vascular biology and the possible conservation of their extravascular functions in endothelial cell biology. Recent findings Membrane-anchored proteases belonging to the serine or metalloprotease families contain amino- or carboxy-terminal domains which serve to tether their extracellular protease domains directly at the plasma membrane. This architecture enables protease function and substrate repertoire to be regulated through dynamic localization in distinct areas of the cell membrane. These proteases are proving to be key components of the cell machinery for regulating vascular permeability, generation of vasoactive peptides, receptor tyrosine kinase transactivation, extracellular matrix proteolysis and angiogenesis. Summary A complex picture is emerging of the interdependence between membrane-anchored protease localization and function that may provide a mechanism for precise coordination of extracellular signals and intracellular responses through communication with the cytoskeleton and with cellular signaling molecules.

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Shedding of epithin/PRSS14 is induced by TGF-β and mediated by tumor necrosis factor-α converting enzyme

Cited by 12 publications

References 32 publications

Impact of suppression of tumorigenicity 14 (ST14)/serine protease 14 (Prss14) expression analysis on the prognosis and management of estrogen receptor negative breast cancer

Impact of suppression of tumorigenicity 14 (ST14)/serine protease 14 (Prss14) expression analysis on the prognosis and management of estrogen receptor negative breast cancer

The down regulation of megalin/LRP2 by transforming growth factor beta (TGF-β1) is mediated by the SMAD2/3 signalling pathway

Membrane-anchored proteases in endothelial cell biology

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