Research Database PMU-SQQUID

PMU-Authors

Abstract

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.

Useful keywords (using NLM MeSH Indexing)

Adenocarcinoma/genetics*

Adenocarcinoma/pathology

Amino Acid Sequence

Animals

Breast Neoplasms/genetics*

Breast Neoplasms/pathology

Caenorhabditis elegans/chemistry

Caenorhabditis elegans/genetics

Calcium-Binding Proteins/genetics*

Calcium-Binding Proteins/metabolism

Calcium-Binding Proteins/pharmacology*

Cell Count

Cell Line, Tumor

Cell Movement/drug effects*

Cytoskeleton/drug effects

Cytoskeleton/ultrastructure

Fluorescent Antibody Technique

Gene Expression Regulation, Neoplastic

Humans

Melanoma, Experimental/genetics*

Melanoma, Experimental/pathology

Mice

Microfilament Proteins

Microscopy, Video/methods

Molecular Sequence Data

Neoplasm Metastasis

Recombinant Fusion Proteins/genetics

Recombinant Fusion Proteins/metabolism

Recombinant Fusion Proteins/pharmacology

Repetitive Sequences, Amino Acid

Sequence Alignment

Sequence Homology, Amino Acid

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