Molecular mechanisms of invadopodium formation

By H. Yamaguchi, M. Lorenz, S. Kempiak, C. Sarmiento, Salvatore J Coniglio, M. Symons, J. Segall, R. Eddy, H. Miki, T. Takenawa and 1 more. Journal of Cell Biology, 2005

624 citations recorded by the source corpus.

Invadopodia are actin-rich membrane protrusions with a matrix degradation activity formed by invasive cancer cells. We have studied the molecular mechanisms of invadopodium formation in metastatic carcinoma cells. Epidermal growth factor (EGF) receptor kinase inhibitors blocked invadopodium formation in the presence of serum, and EGF stimulation of serum-starved cells induced invadopodium formation. RNA interference and dominant-negative mutant expression analyses revealed that neural WASP (N-WASP), Arp2/3 complex, and their upstream regulators, Nck1, Cdc42, and WIP, are necessary for invadopodium formation. Time-lapse analysis revealed that invadopodia are formed de novo at the cell periphery and their lifetime varies from minutes to several hours. Invadopodia with short lifetimes are motile, whereas long-lived invadopodia tend to be stationary. Interestingly, suppression of cofilin expression by RNA interference inhibited the formation of long-lived invadopodia, resulting in formation of only short-lived invadopodia with less matrix degradation activity. These results indicate that EGF receptor signaling regulates invadopodium formation through the N-WASP–Arp2/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia.

Subfields: Atomic and Molecular Physics, and Optics, Cell Biology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/185f5e318dbb5e0a93003a06e416d1cffac8655d

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Citations in the corpus

The many faces of actin: matching assembly factors with cellular structures (2007, background): “N-WASP and the Arp2/3 complex are enriched in, and are required for, invadopodia assembl”
Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. (2006, background): “Nonetheless, current understanding of molecular mechanisms that govern invadopodia formation has been limited to the early events of actin polymerization induction through the Arp2/3 complex that drives invadopodia initiation (14).”
EMT, the cytoskeleton, and cancer cell invasion (2009, positive): “Elimination of the activities of Rac1 or Cdc42 results in a reduction of invadopodia formation in glioma cells and mammary carcinoma cells, respectively [197, 215].”
Mechanics, malignancy, and metastasis: The force journey of a tumor cell (2009, background): “While the structure and molecular composition of invadopodia remain incompletely understood, from these studies it is now clear that formation of these structures requires highly localized actin polymerization and the coordinated action of multiple actin binding proteins, including cofillin, Arp2/3,”
The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function (2011, neutral): “Induction of podosomes and invadopodia Many studies have shown that stimulation with growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGFβ) and epidermal growth factor (EGF), induces podosome or invadopodium formation in normal and cancer cells, resp”