The role of calponin in the gene profile of metastatic cells: inhibition of metastatic cell motility by multiple calponin repeats.
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 CLIK(23) 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 CLIK(23) 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.
Lener
Thomas
T
Institute of Molecular Biology, Department of Cell Biology, Austrian Academy of Sciences, Billrothstrasse 11, A-5020, Salzburg, Austria.
Burgstaller
Gerald
G
Gimona
Mario
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D002452:Cell Count; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008840:Microfilament Proteins; D018715:Microscopy, Video / Q000379:methods; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000096985:Calponins
D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; D000096985:Calponins