Regulation of MT1-MMP activity by β-catenin in MDCK non-cancer and HT1080 cancer cells.
Past studies on β-catenin in cancer cells focused on nuclear localized β-catenin and its involvement in the Wnt pathway. Our goal here was to investigate the function of β-catenin in both the cytoplasm and nucleus on the regulation of MT1-MMP expression and activity. We found that β-catenin in MDCK non-cancer cells inhibited the cell surface localization of MT1-MMP, and thus its proteolytic activity on pro-MMP2 activation, via direct interaction with the 18-amino-acid cytoplasmic tail of MT1-MMP in the cytoplasm. In contrast, β-catenin in HT1080 cancer cells enhanced the activity of MT1-MMP by entering the nucleus and activating transcription factor Tcf-4/Lef, and elevating the level of MT1-MMP protein. We also found that enhancement of cell growth in three-dimensional (3-D)/two-dimensional (2-D) type I collagen gels and of cell migration by MT1-MMP were inhibited by β-catenin in MDCK cells, whereas these functions were enhanced in HT1080 cells. In addition, regulation of MT1-MMP by β-catenin involved E-cadherin in MDCK cells and Wnt-3a in HT1080 cells. Taken together, our results present a differential effect of cytoplasmic and nuclear β-catenin on MT1-MMP activity in non-cancer cells versus cancer cells. These differences were most probably due to different subcellular locations and different involved pathways of β-catenin in these cells.
Liu
Ping
P
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Yang
Jianbo
J
Pei
Jing
J
Pei
Duanqing
D
Wilson
Michael J
MJ
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000201:enzymology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D003593:Cytoplasm / Q000201:enzymology; D004285:Dogs; D004792:Enzyme Precursors / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology*; D018093:Gelatinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology*; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; D015820:Cadherins; D004792:Enzyme Precursors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin; D018093:Gelatinases; C069860:progelatinase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14