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:3.4.24.35 (
matrix metalloproteinase 9
)
2,207
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Collagen type IV degradation results in disruption and breakdown of the normal basement membrane architecture, a key process in the initiation of tumor microinvasion into the connective tissue.
PACE4
, a proprotein convertase, activates membrane type matrix metalloproteinases (MT-MMPs) that in turn process
collagenase type IV
. Because
PACE4
is overexpressed in skin carcinomas and in vitro overexpression of
PACE4
resulted in enhanced invasiveness, we investigated whether or not in vivo
PACE4
expression leads to the acquisition of invasiveness and increased tumorigenesis. Two transgenic mouse lines were designed by targeting
PACE4
to the epidermal basal keratinocytes. Transgenic keratinocytes showed increased processing of MT1-MMP and MT2-MMP resulting in
collagenase IV
activation and collagen type IV degradation. Higher collagenolytic activity partially disrupted normal basement membrane architecture favoring epithelial endophytic growth into the dermis and accelerating invasion and metastasis after chemical carcinogenesis.
PACE4
overexpression resulted in enhanced susceptibility to carcinogenesis and tumor progression pointing to a new target for blocking tumor cell invasiveness.
...
PMID:PACE4 expression in mouse basal keratinocytes results in basement membrane disruption and acceleration of tumor progression. 1610 82
