Cell-penetrating peptides with intracellular actin-remodeling activity in malignant fibroblasts.
Cell-penetrating peptides can cross cell membranes and are commonly seen as biologically inert molecules. However, we found that some cell-penetrating peptides could remodel actin cytoskeleton in oncogene-transformed NIH3T3/EWS-Fli cells. These cells have profound actin disorganization related to their tumoral transformation. These arginine- and/or tryptophan-rich peptides could cross cell membrane and induce stress fiber formation in these malignant cells, whereas they had no perceptible effect in non-tumoral fibroblasts. In addition, motility (migration speed, random motility coefficient, wound healing) of the tumor cells could be decreased by the cell-permeant peptides. Although the peptides differently influenced actin polymerization in vitro, they could directly bind monomeric actin as determined by NMR and calorimetry studies. Therefore, cell-penetrating peptides might interact with intracellular protein partners, such as actin. In addition, the fact that they could reverse the tumoral phenotype is of interest for therapeutic purposes.
Delaroche
Diane
D
Laboratoire des Biomolécules, Université Pierre et Marie Curie, CNRS, 4 place Jussieu, F-75005 Paris, France.
Cantrelle
François-Xavier
FX
Subra
Frédéric
F
Van Heijenoort
Carine
C
Guittet
Eric
E
Jiao
Chen-Yu
CY
Blanchoin
Laurent
L
Chassaing
Gérard
G
Lavielle
Solange
S
Auclair
Christian
C
Sagan
Sandrine
S
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D048430:Cell Shape; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology* / Q000502:physiology*; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism / Q000648:ultrastructure; D060589:Zyxin
D000199:Actins; D008667:Metalloproteins; D010455:Peptides; C498285:Zyx protein, mouse; D060589:Zyxin