beta-Catenin/Wnt signaling regulates expression of the membrane type 3 matrix metalloproteinase in gastric cancer.
Activation of Wnt signaling through beta-catenin dysregulation occurs in numerous human tumors, including gastric cancer. The specific consequences of Wnt signaling in gastric cancer, however, are not well characterized. This study shows that the introduction of mutant beta-catenin into gastric cancer cell lines by adenoviral infection enhances invasiveness and proliferation and up-regulates the expression of the gene encoding the matrix metalloproteinase (MMP) family member membrane type 3 MMP (MT3-MMP). Up-regulation of MT3-MMP is critical to the invasive phenotype as shown by small interfering RNA (siRNA) studies. Immunohistochemical staining also showed that MT3-MMP was highly expressed in gastric cancers with activating beta-catenin mutations. These observations suggest that Wnt activation may contribute to gastric cancer progression by increasing the invasiveness of neoplastic cells in the stomach via up-regulation of MT3-MMP expression.
Lowy
Andrew M
AM
Department of Surgery, Division of Surgical Oncology, Barrett Cancer Center, University of Cincinnati, Cincinnati, OH 45219, USA. andrew.lowy@uc.edu
Clements
Wilson M
WM
Bishop
John
J
Kong
Ling
L
Bonney
Tera
T
Sisco
Karena
K
Aronow
Bruce
B
Fenoglio-Preiser
Cecilia
C
Groden
Joanna
J
D000818:Animals; D019556:COS Cells; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053513:Matrix Metalloproteinase 16; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C507102:MMP16 protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D053513:Matrix Metalloproteinase 16; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated