Evidence for protein 4.1B acting as a metastasis suppressor.
We compared a non-metastasising sarcoma cell population with three related populations of increasing metastatic potential. The metastatic cells in vitro exhibited a significantly reduced incidence of actin stress fibres but enhanced motility and chemotaxis. We also investigated gene expression underlying progression to a metastatic phenotype by performing a microarray analysis of the four sarcoma populations. We identified a subset of genes with significantly altered expression levels between non-metastasising and metastasising cells in tissue culture and in primary tumours. One such gene, encoding protein 4.1B, is downregulated in the metastatic sarcoma populations. To investigate possible roles of 4.1B in the mechanisms of metastasis, we used RNA interference (RNAi) to reduce its expression in the non-metastatic cells. Cells with reduced 4.1B expression displayed an altered F-actin morphology, with significantly fewer stress fibres. We also found that the 4.1B RNAi cells migrated at twice the speed of the untreated cells. Metastatic cells exogenously expressing 4.1B migrated at half the speed of control metastatic cells and displayed suppressed chemotaxis. Therefore, we propose that the reduction of 4.1B in the metastatic cells promotes the metastatic phenotype as a result of inducing a loss of actin stress fibres and a concomitant increase in cell motility.
Cavanna
Tamara
T
Light Microscopy, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
Pokorná
Eva
E
Veselý
Pavel
P
Gray
Colin
C
Zicha
Daniel
D
D000818:Animals; D002461:Cell Line, Transformed; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D002633:Chemotaxis; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D040081:Protein Array Analysis; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012509:Sarcoma / Q000473:pathology; D022502:Stress Fibers / Q000378:metabolism; D008840:Microfilament Proteins
D049452:Green Fluorescent Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C116887:EPB41L3 protein, human; D008840:Microfilament Proteins