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Regulation of MT1‐MMP activity by β‐catenin in MDCK non‐cancer and HT1080 cancer cells
Author(s) -
Liu Ping,
Yang Jianbo,
Pei Jing,
Pei Duanqing,
Wilson Michael J.
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22292
Subject(s) - ht1080 , cancer cell , cytoplasm , microbiology and biotechnology , wnt signaling pathway , cell , catenin , matrix metalloproteinase , cell culture , chemistry , biology , cancer , signal transduction , biochemistry , genetics
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. J. Cell. Physiol. 225: 810–821, 2010. © 2010 Wiley‐Liss, Inc.