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

Han Zhang, Xunsheng Chen, Wendy B. Bollag, Roni J. Bollag, Daniel J. Sheehan, Catherine S. Chew

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)372-385
Number of pages14
JournalPhysiological Genomics
Volume38
Issue number3
DOIs
StatePublished - Aug 1 2009

Fingerprint

Lipoma
Cell Movement
Focal Adhesions
Zyxin
Molecular Motor Proteins
Genes
Cell Line
Neoplasms
Gene Knockout Techniques
Phosphoproteins
Microarray Analysis
Cell Adhesion
Wound Healing
Small Interfering RNA
Actins
Carrier Proteins
Proteins
Up-Regulation
Fibroblasts
Neoplasm Metastasis

Keywords

  • LIM and SH3 domain protein
  • Lipoma preferred partner
  • Mouse embryonic fibroblasts
  • Tumor formation
  • Zyxin

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Lasp1 gene disruption is linked to enhanced cell migration and tumor formation. / Zhang, Han; Chen, Xunsheng; Bollag, Wendy B.; Bollag, Roni J.; Sheehan, Daniel J.; Chew, Catherine S.

In: Physiological Genomics, Vol. 38, No. 3, 01.08.2009, p. 372-385.

Research output: Contribution to journalArticle

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