Physiol. Genomics AJP: Heart and Circulatory Physiology
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Physiol. Genomics 38: 372-385, 2009. First published June 16, 2009; doi:10.1152/physiolgenomics.00048.2009
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Received 11 March 2009; accepted in final form 10 June 2009.
Physiological Genomics 38:372-385 (2009)
1094-8341/09 $8.00 © 2009 American Physiological Society

Lasp1 gene disruption is linked to enhanced cell migration and tumor formation

Han Zhang 1,4, Xunsheng Chen 1, Wendy B. Bollag 1,2, Roni J. Bollag 3, Daniel J. Sheehan 2,3 and Catherine S. Chew 1,2

1 Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia
2 Department of Medicine, Medical College of Georgia, Augusta, Georgia
3 Department of Pathology, Medical College of Georgia, Augusta, Georgia
4 Departments of Gastroenterology and Blood Transfusion, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China

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.

LIM and SH3 domain protein; mouse embryonic fibroblasts; tumor formation; zyxin; lipoma preferred partner






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