STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter
-
Constance Zugowski
Abstract
Aberrant activation of STAT3 in colorectal carcinoma (CRC) tissue is correlated with elevated expression of matrix metalloproteinase-1 (MMP-1). We analyzed transcriptional regulation of the human MMP-1 promoter in CRC cells by tyrosine phosphorylated (pY-) STAT3. One of six putative STAT binding elements within a 4.3 kb MMP-1 trancriptional promoter fragment showed a particular high affinity for STAT3 in vitro. However, the most profound regulatory influence on MMP-1 promoter activity resides in a proximal region relative to the transcriptional start, bearing a pair of putative binding sites for STAT3 and AP-1. Mutational analysis of the combined STAT3/AP-1 recognition element revealed that the integrity of the STAT3 binding site is necessary, but not sufficient for both DNA interaction and transcriptional regulation by activated STAT3. Instead, the adjacent AP-1 site was essential for pY-STAT3-mediated transcription on the MMP-1 promoter. DNA-protein binding assays provided strong evidence for complex formation of STAT3 and c-Jun governed by protein-protein contacts. We observed striking coincidence for concerted aberrant activation of both STAT3 and AP-1 in human colon cancer specimens. This finding supports the notion that the combination of inappropriate STAT3 and AP-1 activities drives elevated MMP-1 expression and tissue invasion in colorectal cancer and is of clinical relevance.
©2011 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Review
- Recent insights into regulation of transcription by RNA polymerase III and the cellular functions of its transcripts
- Genes and Nucleic Acids
- Post-transcriptional regulation of human cathepsin L expression
- Protein Structure and Function
- In vitro conversion and seeded fibrillization of posttranslationally modified prion protein
- Synthesis of recombinant high density lipoprotein with apolipoprotein A-I and apolipoprotein A-V
- Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1
- Molecular Medicine
- Inhibition of AP-1 suppresses cervical cancer cell proliferation and is associated with p21 expression
- STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter
- Cell Biology and Signaling
- TGFβ1 suppresses vascular smooth muscle cell motility by expression of N-cadherin
- Renal pro-apoptotic proteins are reduced by growth hormone resistance but not by visceral fat removal
- Proteolysis
- Inhibition of Staphylococcus aureus cysteine proteases by human serpin potentially limits staphylococcal virulence
Articles in the same Issue
- Review
- Recent insights into regulation of transcription by RNA polymerase III and the cellular functions of its transcripts
- Genes and Nucleic Acids
- Post-transcriptional regulation of human cathepsin L expression
- Protein Structure and Function
- In vitro conversion and seeded fibrillization of posttranslationally modified prion protein
- Synthesis of recombinant high density lipoprotein with apolipoprotein A-I and apolipoprotein A-V
- Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1
- Molecular Medicine
- Inhibition of AP-1 suppresses cervical cancer cell proliferation and is associated with p21 expression
- STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter
- Cell Biology and Signaling
- TGFβ1 suppresses vascular smooth muscle cell motility by expression of N-cadherin
- Renal pro-apoptotic proteins are reduced by growth hormone resistance but not by visceral fat removal
- Proteolysis
- Inhibition of Staphylococcus aureus cysteine proteases by human serpin potentially limits staphylococcal virulence
