The role of calponin in the gene profile of metastatic cells: inhibition of metastatic cell motility by multiple calponin repeats

FEBS Letters

Burgstaller, Gerald¹  Gimona, Mario¹  Lener, Thomas¹ 

[1]Institute of Molecular Biology, Department of Cell Biology, Austrian Academy of Sciences, Billrothstrasse 11, A-5020 Salzburg, Austria

关键词: Calponin repeat;    Cell motility;    Metastasis;    Melanoma;    Adenocarcinoma;    Actin turnover;    CLIK23 repeat;    23 amino acid residue calponin-like repeat;    F-actin;    filamentous actin;    GFP;    green fluorescent protein;    CaP;    calponin;    PFA;    paraformaldehyde;    h1;    h2;    genetic variants of CaP;   

DOI  :  10.1016/S0014-5793(03)01401-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Metastasis of diseased cells is the basic event leading to death in individuals with cancer. Establishment of metastasis requires that tumour cells migrate from the site of the primary tumour into the circulation system, escape from the vasculature and form secondary tumours at novel sites. These processes depend to a large degree on cytoskeletal remodeling. We show here that multiple copies of the short actin-binding module CLIK²³ from human or Caenorhabditis elegans calponin proteins effectively inhibit cell motility on two dimensional matrices and suppress soft agar colony formation of metastatic melanoma and adenocarcinoma cells of murine and human origin. Ectopic expression of CLIK²³ modules for 30 days results in the formation of multinucleated cells. The repeat displays true modular behaviour, resulting in increased cytoskeletal effects in direct correlation with the increase in number of modules. Our results demonstrate that the role of calponin in the signature profile of metastasising cells is that of a mechanical stabiliser of the actin cytoskeleton, which interferes with actin turnover by binding at a unique interface along the actin filament.

【 授权许可】

Unknown