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Role of Lasp‐1 in regulation of cell motility and migration
Author(s) -
Zhang Han,
Chen Xunsheng,
Chew Catherine S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1218.6
Subject(s) - focal adhesion , cell migration , motility , microbiology and biotechnology , lim domain , cell adhesion , extracellular matrix , biology , cell , chemistry , signal transduction , genetics , gene , transcription factor , zinc finger
Lasp‐1 is a phosphorylated signaling protein that is over‐expressed in several cancers. Lasp‐1 is present in focal adhesions (FAs) and binds to the FA protein, zyxin. In cancer cell lines, depletion of Lasp‐1 inhibits cell migration and depletes zyxin from FAs. To define the effects of loss of Lasp‐1 in normal cells, we compared responses of mouse embryonic fibroblasts (MEFs) from Lasp‐1 −/− and wild type (WT) littermates. Lasp‐1 −/− MEFs migrated faster in wound‐healing assays and attached more rapidly to extracellular matrices. FA numbers were significantly increased in Lasp‐1 −/− MEFs, whereas zyxin localization was unchanged. Zyxin expression was also unchanged, suggesting that zyxin redistributes to FA from other cellular compartment(s). Interestingly, zyxin −/− MEFs have also been found to migrate faster than WT MEFs, and Mena/VASP proteins are lost from FAs in these MEFs. We hypothesize that Lasp‐1 and zyxin, and possibly other focal adhesion proteins, interact to regulate normal cell migration. The loss of either Lasp‐1 or zyxin disturbs this balance allowing for increased migration and attachment. The striking contrast in the functional effects of loss of Lasp‐1 in nontransformed cells as compared to cancer cell lines identifies distinct differences in regulatory mechanisms associated with motility and attachment in these cellular models. (Supported by NIH R01 DK31900).