The actin-bundling protein fascin stabilizes actin in invadopodia and potentiates protrusive invasion.
Fascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types. Fascin forms stable actin bundles with slow dissociation kinetics in vitro and is regulated by phosphorylation of serine 39 by protein kinase C (PKC). Cancer cells use invasive finger-like protrusions termed invadopodia to invade into and degrade extracellular matrix. Invadopodia have highly dynamic actin that is assembled by both Arp2/3 complex and formins; they also contain components of membrane trafficking machinery such as dynamin and cortactin and have been compared with focal adhesions and podosomes. We show that fascin is an integral component of invadopodia and that it is important for the stability of actin in invadopodia. The phosphorylation state of fascin at S39, a PKC site, contributes to its regulation at invadopodia. We further implicate fascin in invasive migration into collagen I-Matrigel gels and particularly in cell types that use an elongated mesenchymal type of motility in 3D. We provide a potential molecular mechanism for how fascin increases the invasiveness of cancer cells, and we compare invadopodia with invasive filopod-like structures in 3D.
Li
Ang
A
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, Scotland, UK.
Dawson
John C
JC
Forero-Vargas
Manuel
M
Spence
Heather J
HJ
Yu
Xinzi
X
König
Ireen
I
Anderson
Kurt
K
Machesky
Laura M
LM
D000199:Actins / Q000378:metabolism*; D015153:Blotting, Western; D002264:Carboxylic Acids; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D021961:Cell Membrane Structures / Q000378:metabolism*; D003094:Collagen; D004338:Drug Combinations; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D007797:Laminin; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011509:Proteoglycans; D034741:RNA, Small Interfering / Q000235:genetics
D000199:Actins; D002264:Carboxylic Acids; D002352:Carrier Proteins; D004338:Drug Combinations; D007797:Laminin; D008840:Microfilament Proteins; C436864:Oregon Green 488 carboxylic acid; D011509:Proteoglycans; D034741:RNA, Small Interfering; C059485:matrigel; C020324:fascin; D003094:Collagen; D011493:Protein Kinase C