Synthetic polyamines promote rapid lamellipodial growth by regulating actin dynamics

Nedeva, Iliana; Koripelly, Girish; Caballero, David; Chièze, Lionel; Guichard, Bérangère; Romain, B.; Pencreach, Erwan; Lehn, Jean-Maríe; Carlier, Marie‐France; Riveline, Daniel

doi:10.1038/ncomms3165

Cited by 21 publications

(25 citation statements)

References 37 publications

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“…The slower turn-over of actin filaments in the motility assay suggested that in vivo lamellipodial actin networks should also turn-over more slowly in the presence of polyamines, which was confirmed by measuring retrograde flow in cells. 18 Finally, we demonstrated that actin nucleation was facilitated in vitro in the presence of capping proteins. So the molecular picture in vivo combines 2 effects: the stabilization of the lamellipodia over time together with the facilitated growth of the actin network at the cell border.…”

Section: Effects Of Synthetic Polyaminesmentioning

confidence: 98%

“…Indeed, actin plays a key role in motility and in cell division: we propose that BPAs/ MPAs would lead to a decrease in cell motility (see our paper 18 for the decreased migration in Boyden chamber) and to a delay in the proliferation rate. Also, it was recently shown that BPAs have a strong inhibitory effect on the transformation of cancerassociated fibroblasts into myofibroblasts, a key step in tumor progression.…”

Section: Application In Cancer: Reduced Motility and Delayed Divisionmentioning

confidence: 99%

“…18 Their direct and specific effect on actin was demonstrated by in vivo experiments with inhibitors and in vitro actin polymerization assays. We have shown that the compounds slow down filament elongation at barbed ends specifically, but do not affect pointed end growth.…”

Section: Synthetic Polyamines As New Agents With Broad Applicationmentioning

confidence: 99%

“…Standard compounds targeted to the actin cytoskeleton and their effects. For more details, see associated references in 18 .…”

Section: Growth Of Lamellipodia: De Novo Extension With Formation Of mentioning

confidence: 99%

“…19 Based on these structures, noncyclic branched polyamines were designed and synthesized for exploration of their effect on actin. 18,20 Both cyclic and branched polyamines of different sizes affected actin assembly similarly with affinities that depended on their size. Here we present 2 compounds that proved the most efficient ones in our study: (i) macrocyclic polyamines C 7 N 6 MPA (MPAs), presenting 2 dipropylene triamine subunits linked by 2 aliphatic 7-carbon chains (Fig.…”

Section: Synthetic Polyamines As New Agents With Broad Applicationmentioning

confidence: 99%

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Synthetic polyamines: new compounds specific to actin dynamics for mammalian cell and fission yeast

et al. 2014

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Actin is a major actor in the determination of cell shape. On the one hand, site-directed assembly/disassembly cycles of actin filaments drive protrusive force leading to lamellipodia and filopodia dynamics. Force produced by actin similarly contributes in membrane scission in endocytosis or Golgi remodeling. On the other hand, cellular processes like adhesion, immune synapse, cortex dynamics or cytokinesis are achieved by combining acto-myosin contractility and actin assembly in a complex and not fully understood manner. New chemical compounds are therefore needed to disentangle acto-myosin and actin dynamics. We have found that synthetic, cell permeant, short polyamines are promising new actin regulators in this context. They generate growth and stabilization of lamellipodia within minutes by slowing down the actin assembly/disassembly cycle and facilitating nucleation. We now report that these polyamines also slow down cytokinetic ring closure in fission yeast. This shows that these synthetic compounds are active also in yeasts, and these experiments specifically highlight that actin depolymerization is involved in the ring closure. Thus, synthetic polyamines appear to be potentially powerful agents in a quantitative approach to the role of actin in complex processes in cell biology, developmental biology and potentially cancer research.

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Section: Effects Of Synthetic Polyaminesmentioning

confidence: 98%

Section: Application In Cancer: Reduced Motility and Delayed Divisionmentioning

confidence: 99%

Section: Synthetic Polyamines As New Agents With Broad Applicationmentioning

confidence: 99%

“…Standard compounds targeted to the actin cytoskeleton and their effects. For more details, see associated references in 18 .…”

Section: Growth Of Lamellipodia: De Novo Extension With Formation Of mentioning

confidence: 99%

Section: Synthetic Polyamines As New Agents With Broad Applicationmentioning

confidence: 99%

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Synthetic polyamines: new compounds specific to actin dynamics for mammalian cell and fission yeast

et al. 2014

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Polyamine signal through gap junctions: A key regulator of proliferation and gap‐junction organization in mammalian tissues?

2016

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We propose that interaction rules derived from polyamine exchange in connected cells may explain the spatio-temporal organization of gap junctions observed during tissue regeneration and tumorigenesis. We also hypothesize that polyamine exchange can be considered as signal that allows cells to sense the proliferation status of their neighbors. Polyamines (putrescine, spermidine, and spermine) are indeed small aliphatic polycations that serve as fuels to sustain elevated proliferation rates of the order observed in cancer cells. Based on recent reports, we consider here that polyamines can be exchanged through gap junction channels between mammalian cells. Such intercellular exchange of polyamines has critical consequences on the local control of growth. In line with this hypothesis, the complex protein network that keeps polyamine levels finely tuned in mammalian cells can translate polyamine efflux or influx into integrated signals controlling transcription, translation, and cell communications.

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Synthetic Polyamine BPA‐C8 Inhibits TGF‐β1‐Mediated Conversion of Human Dermal Fibroblast to Myofibroblasts and Establishment of Galectin‐1‐Rich Extracellular Matrix in Vitro

Mifkova¹,

Kodet²,

Szabó³

et al. 2014

ChemBioChem

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Cancer-associated fibroblasts (CAFs) play a role in the progression of malignant tumors. They are formed by conversion of fibroblasts to smooth muscle α-actin-positive (SMA-positive) myofibroblasts. Polyamines are known to change the arrangement of the actin cytoskeleton by binding to the anionic actin. We tested the effect of the synthetic polyamine BPA-C8 on the transition of human dermal fibroblasts to myofibroblasts induced either by TGF-β1 alone or by TGF-β1 together with adhesion/growth-regulatory galectin-1. Pre-existing CAFs, myofibroblasts from pancreatitis, and rat smooth muscle cells were also exposed to BPA-C8. BPA-C8 impaired myofibroblast formation from activated fibroblasts, but it had no effect on cells already expressing SMA. BPA-C8 also reduced the occurrence of an extracellular matrix around the activated fibroblasts. The reported data thus extend current insights into polyamine activity, adding interference with tumor progression to the tumor-promoting processes warranting study.

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Synthetic polyamines promote rapid lamellipodial growth by regulating actin dynamics

Cited by 21 publications

References 37 publications

Synthetic polyamines: new compounds specific to actin dynamics for mammalian cell and fission yeast

Synthetic polyamines: new compounds specific to actin dynamics for mammalian cell and fission yeast

Polyamine signal through gap junctions: A key regulator of proliferation and gap‐junction organization in mammalian tissues?

Synthetic Polyamine BPA‐C8 Inhibits TGF‐β1‐Mediated Conversion of Human Dermal Fibroblast to Myofibroblasts and Establishment of Galectin‐1‐Rich Extracellular Matrix in Vitro

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