SUNDAY, DECEMBER 4- Late Abstracts 1 - Molecular Biology of the ...

SUNDAY
calcium release and actin polymerization. Taken together, the data implicate FPR1 in mediating
lens cell migration, a critical event for lens development and maintenance.
2055
PRL-3 promotes migration and invasion by up-regulating MMP-7 in human colorectal
cancer cells.
Y-M. Han 1 , S-K. Lee 2 , D-S. Sin 2 , Y-R. Ha 2 , J. Kim 2 , C-W. Lee 3 ; 1 University of Science and
Technology, Daejeon, Korea, 2 Laboratory of Chemical Biology and Genomics, Korea Research
Institute of Bioscience and Biotechnology, Daejeon, Korea, 3 Bio-Evaluation Center, Korea
Research Institute of Bioscience and Biotechnology, Chungbuk, Korea
PRL-3, a member of a subgroup of protein tyrosine phosphatases (PTPs) that can stimulate the
degradation of the extracellular matrix, is over-expressed in metastatic colorectal cancer relative
to primary tumors. To determine whether PRL-3-induced enhancement of migration and
invasion is dependent on the expression of matrix metalloproteases (MMPs), PRL-3 was
expressed in DLD-1 human colorectal cancer cells. The motility, migration and invasion
characteristics of the cells were examined and metastasis to the lung was confirmed in a nude
mouse using PRL-3-overexpressing DLD-1 cells [DLD-1 (PRL-3)]. Migration and invasion of the
cells were inhibited by phosphatase and farnesyl transferase inhibitors. Expression of MMPs
was enhanced 3- to 10-fold in comparison to control cells, and migration and invasion were
partially inhibited by siRNA knockdown of MMP-2, -13, or -14. Importantly, siRNA knockdown of
MMP-7 completely inhibited the migration and invasion of DLD-1 (PRL-3) cells, while
overexpression of MMP-7 increased migration. The expression of MMP-7 was also downregulated
by phosphatase and farnesyl transferase inhibitors. It was found that PRL-3 induced
MMP-7 through oncogenic pathways including PI3K/AKT and ERK, and that there is a
relationship between the expression of PRL-3 and MMP-7 in human tumor cell lines. The
expression of MMP-13 and MMP-14 was very sensitive to the inhibition of farnesyl transferase;
however, the migration and invasion of DLD-1 (PRL-3) cells did not strongly depend on the
expression of MMP-13 or -14. These results suggest that the migration and invasion of PRL-3expressing
colorectal cancer cells depends primarily on the expression of MMP-7.
2056
Serine phosphorylation in paxillin is important for focal adhesion formation during cell
adhesion onto collagen type I.
T. Kwak 1 , J. W. Lee 1 ; 1 Department of Pharmacy, Research Institute of Pharmaceutical
Sciences, College of Pharmacy, Seoul National University, Seoul, Korea
Integrin-mediated adhesion to extracellular matrix proteins is dynamically regulated during
morphological change and cell migration. Upon cell adhesion, protein-protein interaction at focal
adhesions consisting of FAK, talin, paxillin, and others, plays major roles in regulation of cell
morphogenesis and migration. Although phosphorylation at tyrosines of paxillin has been well
known to be critically involved in adhesion-mediated signaling, little is known about the
significance of paxillin phosphorylation at serine 85 in cell migration. Here in this study, we
provide evidences that paxillin phosphorylation at serine 85 occurred during HeLa cell adhesion
onto collagen I, being concomitant with FAK and talin phosphorylations. However,
unphosphorylatable mutant S85A paxillin impaired cell spreading, focal adhesion turnover, and
migration toward collagen I but not to serum components. Further, the physical interaction
between paxillin and talin was through the C-terminal tail of talin leading to focal adhesions at
the cell boundary, but S85A paxillin did not bind talin and caused random focal adhesion
formation. Together, these observations suggest that paxillin phosphorylation at Serine 85
depending on cell adhesion is important for interaction with talin and for cell morphological and