Abstract
Carcinogenesis is accompanied by increased protein and activity levels of extracellular cell-surface proteases that are capable of modifying the tumor microenvironment by directly cleaving the extracellular matrix, as well as activating growth factors and proinflammatory mediators involved in proliferation and invasion of cancer cells, and recruitment of inflammatory cells. These complex processes ultimately potentiate neoplastic progression leading to local tumor cell invasion, entry into the vasculature, and metastasis to distal sites. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression. In this review the knowledge collected over the past two decades about the molecular mechanisms underlying the pro-cancerous properties of selected TTSPs will be summarized. Furthermore, we will discuss how these insights may facilitate the translation into clinical settings in the future by specifically targeting TTSPs as part of novel cancer treatment regimens.
Acknowledgments
This work was supported by a NIH Ruth L. Kirschstein National Research Service Award T32-CA009531 (A.S.M.), NCI NIH RCA60565A (K.L.) and NCI NIH 3R01CA160565-04S grant (K.L., F.A.V.), and NIGMS/NIH grant R25 GM 058905-15 (F.A.V.).
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©2016 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: proteolytic networks across cellular boundaries
- HIGHLIGHT: IPS 2015 – 9TH GENERAL MEETING OF THE INTERNATIONAL PROTEOLYSIS SOCIETY
- A personal journey with matrix metalloproteinases
- Type II transmembrane serine proteases as potential targets for cancer therapy
- Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease
- Dipeptidyl peptidase 9 substrates and their discovery: current progress and the application of mass spectrometry-based approaches
- Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains
- Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors
- Granzyme B inhibits keratinocyte migration by disrupting epidermal growth factor receptor (EGFR)-mediated signaling
- Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1
- Probing catalytic rate enhancement during intramembrane proteolysis
- Human 20S proteasome activity towards fluorogenic peptides of various chain lengths
- Research Articles/Short Communications
- Protein Structure and Function
- Biophysical analysis of three novel profilin-1 variants associated with amyotrophic lateral sclerosis indicates a correlation between their aggregation propensity and the structural features of their globular state
- The potential of the Galleria mellonella innate immune system is maximized by the co-presentation of diverse antimicrobial peptides
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: proteolytic networks across cellular boundaries
- HIGHLIGHT: IPS 2015 – 9TH GENERAL MEETING OF THE INTERNATIONAL PROTEOLYSIS SOCIETY
- A personal journey with matrix metalloproteinases
- Type II transmembrane serine proteases as potential targets for cancer therapy
- Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease
- Dipeptidyl peptidase 9 substrates and their discovery: current progress and the application of mass spectrometry-based approaches
- Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains
- Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors
- Granzyme B inhibits keratinocyte migration by disrupting epidermal growth factor receptor (EGFR)-mediated signaling
- Myeloid conditional deletion and transgenic models reveal a threshold for the neutrophil survival factor Serpinb1
- Probing catalytic rate enhancement during intramembrane proteolysis
- Human 20S proteasome activity towards fluorogenic peptides of various chain lengths
- Research Articles/Short Communications
- Protein Structure and Function
- Biophysical analysis of three novel profilin-1 variants associated with amyotrophic lateral sclerosis indicates a correlation between their aggregation propensity and the structural features of their globular state
- The potential of the Galleria mellonella innate immune system is maximized by the co-presentation of diverse antimicrobial peptides