Collagen XVI induces expression of MMP9 via modulation of AP-1 transcription factors and facilitates invasion of oral squamous cell carcinoma.
Collagen XVI belongs to the family of fibril-associated collagens with interrupted triple helices (FACIT). It is overexpressed during the progression of oral squamous cell carcinoma (OSCC). The present data show a strong collagen XVI-dependent induction of MMP9 and an increase in OSCC cell invasion. We found activated integrin-linked kinase (ILK) in a complex with kindlin-1 and activation of protein kinase B (PKB/Akt) to be responsible for MMP9 induction. Inhibition of the formation of focal adhesions reduced MMP9 expression. Moreover, collagen XVI overexpressing OSCC cell clones (COLXVI cell clones) transfected with vectors containing different MMP9 promoter fragments adjacent to a luciferase reporter revealed an increase in luciferase signal dependent on AP-1 binding sites. Deletion of the AP-1 binding site 98 bp upstream of the reported transcription start site and inhibition of AP-1 with Tanshinone IIA resulted in decreased MMP9 expression. The AP-1 subunit JunB showed differential expression between COLXVI cell clones and mock control cells. Additionally, mass spectrometric analysis of immunoprecipitates revealed that c-Fos interacted strongly with dyskerin in COLXVI cell clones compared to mock controls.
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany ; Center for Medical Biotechnology, BioPark I, Regensburg, Germany.
Konstanze B
KB
Bedal
Department of Orthopaedic Surgery, Experimental Orthopaedics, University Hospital Regensburg, Regensburg, Germany ; Center for Medical Biotechnology, BioPark I, Regensburg, Germany.
Susanne
S
Grässel
Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
Peter J
PJ
Oefner
Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
Joerg
J
Reinders
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany.
Torsten E
TE
Reichert
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany ; Center for Medical Biotechnology, BioPark I, Regensburg, Germany.
Richard
R
Bauer
D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000099200:Scaffold Protein ILK
D003094:Collagen; D020780:Matrix Metalloproteinase 9; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D000099200:Scaffold Protein ILK; C481130:COL16A1 protein, human; C475301:FERMT1 protein, human; C579270:MMP9 protein, human