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)
Hallmarks of cancer cells are uncontrolled proliferation, evasion of apoptosis, angiogenesis, cell invasion, and metastasis, which are driven by oncogenic activation of signaling pathways. Herein, we identify the scaffold protein
CNK1
as a mediator of oncogenic signaling that promotes invasion in human breast cancer and cervical cancer cells. Downregulation of
CNK1
diminishes the invasiveness of cancer cells and correlates with reduced expression of
matrix metalloproteinase 9
(
MMP-9
) and membrane-type 1 MMP (MT1-MMP). Ectopic expression of
CNK1
elevates MT1-MMP promoter activity in a NF-kappaB-dependent manner. Moreover,
CNK1
cooperates with the NF-kappaB pathway, but not with the extracellular signal-regulated protein kinase pathway, to promote cell invasion. Mechanistically,
CNK1
regulates the alternative branch of the NF-kappaB pathway because knockdown of
CNK1
interferes with processing of NF-kappaB2 p100 to p52 and its localization to the nucleus. In agreement with this, the invasion of
CNK1
-depleted cells is less sensitive to RelB downregulation compared with the invasion of control cells. Moreover,
CNK1
-dependent MT1-MMP promoter activation is blocked by RelB siRNA. Thus,
CNK1
is an essential mediator of an oncogenic pathway involved in invasion of breast and cervical cancer cells and is therefore a putative target for cancer therapy.
...
PMID:CNK1 promotes invasion of cancer cells through NF-kappaB-dependent signaling. 2019 85
