Cathepsin E Prevents Tumor Growth and Metastasis by Catalyzing the Proteolytic Release of Soluble TRAIL from Tumor Cell Surface

Kawakubo, Tomoyo; Okamoto, Kuniaki; Iwata, Jun; Shin, Masashi; Okamoto, Yoshiharu; Yasukochi, Atsushi; Nakayama, Keiichi I.; Kadowaki, Tomoko; Tsukuba, Takayuki; Yamamoto, Kazuo

doi:10.1158/0008-5472.can-07-2048

Cited by 82 publications

(80 citation statements)

References 49 publications

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“…However, the observations reported herein for MMP-8, as well as recent findings for other MMP family members (38)(39)(40)(41)(42), clearly indicate that the cancer protective roles of MMPs may be much more relevant than anticipated. These findings will likely be extended to other protease families with multiple components whose expression is dysregulated in cancer (6,24,(43)(44)(45)(46)(47)(48) and emphasize the need to precisely define the complete set of proteases produced by each specific tumor before developing protease inhibitor-based approaches for cancer treatment (6). Finally, the recent development of global systems for profiling proteases in tumor samples (49,50) will contribute to get new insights into the emerging and paradoxical roles of these enzymes as tumor suppressors in cancer.…”

Section: Discussionmentioning

confidence: 97%

Matrix Metalloproteinase-8 Functions as a Metastasis Suppressor through Modulation of Tumor Cell Adhesion and Invasion

Gutiérrez‐Fernández¹,

Fueyo

Folgueras³

et al. 2008

Cancer Research

172

153

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Collagenase-2 (matrix metalloproteinase-8, MMP-8) is an MMP mainly produced by neutrophils and associated with many inflammatory conditions. We have previously described that MMP-8 plays a protective role in cancer through its ability to regulate the inflammatory response induced by carcinogens. Moreover, it has been reported that experimental manipulation of the expression levels of this enzyme alters the metastatic behavior of human breast cancer cells. In this work, we have used mutant mice deficient in MMP-8 and syngenic melanoma and lung carcinoma tumor cells lines overexpressing this enzyme to further explore the putative antimetastatic potential of MMP-8. We report herein that MMP-8 prevents metastasis formation through the modulation of tumor cell adhesion and invasion. Thus, tumor cells overexpressing MMP-8 have an increased adhesion to extracellular matrix proteins, whereas their invasive ability through Matrigel is substantially reduced when compared with control cells. Analysis of MMP-8 in breast cancer patients revealed that the expression of this metalloproteinase by breast tumors correlates with a lower incidence of lymph node metastasis and confers good prognosis to these patients. On this basis, we propose that MMP-8 is a tumor protective factor, which also has the ability to reduce the metastatic potential of malignant cells in both mice and human.

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Section: Discussionmentioning

confidence: 97%

Matrix Metalloproteinase-8 Functions as a Metastasis Suppressor through Modulation of Tumor Cell Adhesion and Invasion

Gutiérrez‐Fernández¹,

Fueyo

Folgueras³

et al. 2008

Cancer Research

172

153

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“…Cathepsin E www.fhc.viamedica.pl inhibits growth of the tumor and inhibits apoptosis in prostate cancer cells by releasing tumor necrosis factor [75]. Furthermore, inhibition of tumor growth by inhibition of angiogenesis, as well as strengthening immunological response, has been found [76].…”

Section: The Role Of Cathepsin E In Pathobiochemistrymentioning

confidence: 99%

Cathepsin E (EC 3.4.23.34) — a review

Chlabicz¹,

Gacko²,

Worowska³

et al. 2012

Folia Histochem Cytobiol.

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Cathepsin E belongs to the third class of enzymes -hydrolases, a subclass of peptide bond hydrolases and a sub-subclass of endopeptidases with aspartic catalytic sites. Cathepsin E is an endopeptidase with substrate specificity similar to that of cathepsin D. In a human organism, cathepsin E occurs in: erythrocytes, thymus, dendritic cells, epithelial M cells, microglia cells, Langerhans cells, lymphocytes, epithelium of gastrointestinal tract, urinary bladder, lungs, osteoclasts, spleen and lymphatic nodes. In human cells, loci of the gene of pre-procathepsin E are located on chromosome 1 in the region 1231-32. The catalytic site of cathepsin E is two residues of aspartic acid -Asp96 and Asn281, occurring in amino acid triads with sequences DTG96-98 and DTG281-283. To date, no particular role of cathepsin E in the metabolism of proteins in normal tissues has been found. However, it is known that there are many documented pathological conditions in which overexpression of cathepsin E occurs.

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“…First-strand cDNA was synthesized from 1 g of total RNA using an oligo(dT) 20 primer and SuperScript III reverse transcriptase (Invitrogen), and quantitative PCR was performed in triplicate by SYBR Green (Bio-Rad) in an iCycler (Bio-Rad). A melting curve was obtained for each PCR product after each run to confirm that the SYBR Green signal corresponded to a unique and specific amplicon.…”

Section: Animals-mating Tgfbr2 Fl/ϩmentioning

confidence: 99%

Transforming Growth Factor-β Regulates Basal Transcriptional Regulatory Machinery to Control Cell Proliferation and Differentiation in Cranial Neural Crest-derived Osteoprogenitor Cells

Iwata

Hosokawa

Sanchez‐Lara

et al. 2010

Journal of Biological Chemistry

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Transforming growth factor-␤ (Tgf-␤) signaling is crucial for regulating craniofacial development. Loss of Tgf-␤ signaling results in defects in cranial neural crest cells (CNCC), but the mechanism by which Tgf-␤ signaling regulates bone formation in CNCC-derived osteogenic cells remains largely unknown. In this study, we discovered that Tgf-␤ regulates the basal transcriptional regulatory machinery to control intramembranous bone development. Specifically, basal transcription factor Taf4b is down-regulated in the CNCC-derived intramembranous bone in Craniofacial skeletal elements are mainly formed by intramembranous ossification through a mechanism that remains relatively uncharacterized. The majority of osteoblasts and chondrocytes in the craniofacial region are derived from cranial neural crest cells (CNCC), 2 which produce the facial skeleton (1, 2). Tgf-␤ signaling plays a crucial role in craniofacial development, and loss of Tgf-␤ signaling in CNCC results in craniofacial skeletal malformations (3, 4). Tgf-␤ transmits signals through a membrane receptor serine/threonine kinase complex that phosphorylates Smad2 and Smad3, and activated Smads form transcriptional complexes with Smad4 and translocate into the nucleus (5). These Tgf-␤ signaling complexes contain other transcription factors and target a variety of genes in an embryonic stage-dependent and cell type-specific manner, but the factors involved in this transcriptional regulatory machinery have yet to be identified. During development, the expression of many genes is associated with changes accompanied by dynamic restructuring of chromatin (6, 7). Recent studies demonstrate that basal transcriptional factors have cell-and promoter-specific functions during embryogenesis (8 -12).RNA polymerase II requires the assembly of a multiprotein complex around the transcriptional start site (13). The general transcriptional factor IID (TFIID) is a large multiprotein transcriptional factor, consisting of the TATA-binding protein and a set of 13-14 TATA-binding protein-associated factors (TAFs), that is responsible for specific binding to the TATA element found in many polymerase II promoters and also demonstrates a coactivator function during transcriptional initiation (14). TAFs are able to regulate gene transcription at multiple steps, with functions in promoter recognition, selective binding to core promoter elements, as well as direct interactions with transcriptional activators (15-17). Mutation and loss of TAFs in yeast and mammalian cells lead to cell cycle arrest and gene-specific transcriptional effects (16). The function of TAFs in gene regulation during embryogenesis has yet to be determined. Here, we show that the interaction between Tgf-␤ signaling and TAFs has a crucial role in regulating CNCC-derived osteogenesis during craniofacial morphogenesis. EXPERIMENTAL PROCEDURES Animals-Mating Tgfbr2fl/ϩ ;Wnt1-Cre with Tgfbr2 fl/fl mice generated Tgfbr2 fl/fl ;Wnt1-Cre conditional null alleles that were genotyped using PCR primers as described previously ...

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Cathepsin E Prevents Tumor Growth and Metastasis by Catalyzing the Proteolytic Release of Soluble TRAIL from Tumor Cell Surface

Cited by 82 publications

References 49 publications

Matrix Metalloproteinase-8 Functions as a Metastasis Suppressor through Modulation of Tumor Cell Adhesion and Invasion

Matrix Metalloproteinase-8 Functions as a Metastasis Suppressor through Modulation of Tumor Cell Adhesion and Invasion

Cathepsin E (EC 3.4.23.34) — a review

Transforming Growth Factor-β Regulates Basal Transcriptional Regulatory Machinery to Control Cell Proliferation and Differentiation in Cranial Neural Crest-derived Osteoprogenitor Cells

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