Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Prostate cancer metastasis to bone is terminal; thus, novel therapies are required to prevent end-stage disease.
Kallikrein-related peptidase 4
(
KLK4
) is a serine protease that is overproduced in localized prostate cancer and is abundant in prostate cancer bone metastases. In vitro,
KLK4
induces tumor-promoting phenotypes; however, the underlying proteolytic mechanism is undefined. The protein topography and migration analysis platform (PROTOMAP) was used for high-depth identification of
KLK4
substrates secreted by prostate cancer bone metastasis-derived PC-3 cells to delineate the mechanism of
KLK4
action in advanced prostate cancer. Thirty-six putative novel substrates were determined from the PROTOMAP analysis. In addition,
KLK4
cleaved the established substrate, urokinase-type plasminogen activator, thus validating the approach.
KLK4
activated
matrix metalloproteinase-1
(
MMP1
), a protease that promotes prostate tumor growth and metastasis.
MMP1
was produced in the tumor compartment of prostate cancer bone metastases, highlighting its accessibility to
KLK4
at this site.
KLK4
further liberated an N-terminal product, with purported angiogenic activity, from thrombospondin-1 (TSP1) and cleaved TSP1 in an osteoblast-derived matrix. This is the most comprehensive analysis of the proteolytic action of
KLK4
in an advanced prostate cancer model to date, highlighting
KLK4
as a potential multifunctional regulator of prostate cancer progression.
...
PMID:Prostate Cancer-Associated Kallikrein-Related Peptidase 4 Activates Matrix Metalloproteinase-1 and Thrombospondin-1. 2737 48
