TY - JOUR
T1 - Lasp1 gene disruption is linked to enhanced cell migration and tumor formation
AU - Zhang, Han
AU - Chen, Xunsheng
AU - Bollag, Wendy B.
AU - Bollag, Roni J.
AU - Sheehan, Daniel J.
AU - Chew, Catherine S.
N1 - Funding Information:
The authors are grateful for the financial support by the National Science Foundation through a TIE project with the Center of Engineering Tribology at Northwestern University and the Air Conditioning and Refrigeration Center, Mechanical and Industrial Engineering Department at the University of Illinois at Urbana-Champaign. The authors would also like to acknowledge the fruitful exchange of ideas and experimental and theoretical findings with Prof. H. S. Cheng and Xiaozhou He from Northwestern University.
PY - 2009/8
Y1 - 2009/8
N2 - Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is overexpressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating nontransformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1-/- mice compared with Lasp1+/+ controls. Embryonic fibroblasts (MEFs) derived from Lasp1-/- mice also migrated more rapidly in vitro. These MEFs characteristically possessed increased focal adhesion numbers and displayed more rapid attachment compared with wild-type MEFs. Differential microarray analyses revealed alterations in message expression for proteins implicated in cell migration, adhesion, and cytoskeletal organization. Notably, the focal adhesion protein, lipoma preferred partner (LPP), a zyxin family member and putative Lasp1 binding protein, was increased about twofold. Because LPP gene disruption reduces cell migration, we hypothesize that LPP plays a role in enhancing the migratory capacity of Lasp1-/- MEFs, perhaps by modifying the subcellular localization of other motility-associated proteins. The striking contrast in the functional effects of loss of Lasp1 in innate cells compared with cell lines reveals distinct differences in mechanisms of motility and attachment in these models.
AB - Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is overexpressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating nontransformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1-/- mice compared with Lasp1+/+ controls. Embryonic fibroblasts (MEFs) derived from Lasp1-/- mice also migrated more rapidly in vitro. These MEFs characteristically possessed increased focal adhesion numbers and displayed more rapid attachment compared with wild-type MEFs. Differential microarray analyses revealed alterations in message expression for proteins implicated in cell migration, adhesion, and cytoskeletal organization. Notably, the focal adhesion protein, lipoma preferred partner (LPP), a zyxin family member and putative Lasp1 binding protein, was increased about twofold. Because LPP gene disruption reduces cell migration, we hypothesize that LPP plays a role in enhancing the migratory capacity of Lasp1-/- MEFs, perhaps by modifying the subcellular localization of other motility-associated proteins. The striking contrast in the functional effects of loss of Lasp1 in innate cells compared with cell lines reveals distinct differences in mechanisms of motility and attachment in these models.
KW - LIM and SH3 domain protein
KW - Lipoma preferred partner
KW - Mouse embryonic fibroblasts
KW - Tumor formation
KW - Zyxin
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U2 - 10.1152/physiolgenomics.00048.2009
DO - 10.1152/physiolgenomics.00048.2009
M3 - Article
C2 - 19531578
AN - SCOPUS:68849118742
SN - 1094-8341
VL - 38
SP - 372
EP - 385
JO - Physiological Genomics
JF - Physiological Genomics
IS - 3
ER -