Scar/WAVE3 contributes to motility and plasticity of lamellipodial dynamics but not invasion in three dimensions.
The Scar (suppressor of cAMP receptor)/WAVE [WASP (Wiskott-Aldrich syndrome protein) verprolin homologous] complex plays a major role in the motility of cells by activating the Arp2/3 complex, which initiates actin branching and drives protrusions. Mammals have three Scar/WAVE isoforms, which show some tissue-specific expression, but their functions have not been differentiated. In the present study we show that depletion of Scar/WAVE3 in the mammalian breast cancer cells MDA-MB-231 results in larger and less dynamic lamellipodia. Scar/WAVE3-depleted cells move more slowly but more persistently on a two-dimensional matrix and they typically only show one lamellipod. However, Scar/WAVE3 appears to have no role in driving invasiveness in a three-dimensional Matrigel™ invasion assay or a three-dimensional collagen invasion assay, suggesting that lamellipodial persistence as seen in two-dimensions is not crucial in three-dimensional environments.
The Beatson Institute for Cancer Research, Garscube Estate, Switchback Rd., Bearsden, Glasgow G61 1BD, UK.
Heather J
HJ
Spence
Paul
P
Timpson
Hao Ran
HR
Tang
Robert H
RH
Insall
Laura M
LM
Machesky
D000230:Adenocarcinoma / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor / Q000166:cytology / Q000648:ultrastructure; D002465:Cell Movement; D048430:Cell Shape; D002999:Clone Cells / Q000166:cytology; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011509:Proteoglycans; D011554:Pseudopodia / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D059008:Time-Lapse Imaging; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D004338:Drug Combinations; D005782:Gels; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering; C120153:WASF3 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; C059485:matrigel; D003094:Collagen