Through activation of the ERK pathway nicotine, in both normal MCF-10A and low malignant breast cancer cells (MCF7), promotes increased motility and invasiveness. Melatonin antagonizes both these effects by inhibiting almost completely ERK phosphorylation. As melatonin has no effect on not-stimulated cells, it is likely that melatonin can counteract ERK-activation only downstream of nicotine-induced activation. This finding suggests that melatonin hampers ERK phosphorylation presumably by targeting a still unknown intermediate factor that connects nicotine stimulation to ERK phosphorylation. Furthermore, downstream of ERK activation, melatonin significantly reduces Fascin and Calpain activation while restoring normal Vinculin levels. Melatonin also counteracts nicotine effects by reshaping the overall cytoskeleton architecture and abolishing invasive membrane protrusion. In addition, melatonin decreases nicotine-dependent ROCK1/ROCK2 activation, thus further inhibiting cell contractility and motility. Melatonin actions are most likely attributable to ERK inhibition, although melatonin could display other ERK-independent effects, namely through a direct modulation of additional molecular and structural factors, including Coronin, Cofilin and cytoskeleton components. This article is protected by copyright. All rights reserved.

Increase in motility and invasiveness of MCF7 cancer cells induced by nicotine is abolished by melatonin through inhibition of ERK phosphorylation / Proietti, Sara; Catizone, Angela; Masiello, Maria Grazia; Dinicola, Simona; Fabrizi, Gianmarco; Minini, Mirko; Ricci, Giulia; Verna, Roberto; Reiter, Russel J; Cucina, Alessandra; Bizzarri, Mariano; Proietti, Catizone UGUALE CONTRIBUTO. - In: JOURNAL OF PINEAL RESEARCH. - ISSN 0742-3098. - STAMPA. - 64:4(2018), pp. 1-17. [10.1111/jpi.12467]

Increase in motility and invasiveness of MCF7 cancer cells induced by nicotine is abolished by melatonin through inhibition of ERK phosphorylation

Proietti, Sara;Catizone, Angela;Masiello, Maria Grazia;Dinicola, Simona;Fabrizi, Gianmarco;Minini, Mirko;Verna, Roberto;Cucina, Alessandra;Bizzarri, Mariano
;
2018

Abstract

Through activation of the ERK pathway nicotine, in both normal MCF-10A and low malignant breast cancer cells (MCF7), promotes increased motility and invasiveness. Melatonin antagonizes both these effects by inhibiting almost completely ERK phosphorylation. As melatonin has no effect on not-stimulated cells, it is likely that melatonin can counteract ERK-activation only downstream of nicotine-induced activation. This finding suggests that melatonin hampers ERK phosphorylation presumably by targeting a still unknown intermediate factor that connects nicotine stimulation to ERK phosphorylation. Furthermore, downstream of ERK activation, melatonin significantly reduces Fascin and Calpain activation while restoring normal Vinculin levels. Melatonin also counteracts nicotine effects by reshaping the overall cytoskeleton architecture and abolishing invasive membrane protrusion. In addition, melatonin decreases nicotine-dependent ROCK1/ROCK2 activation, thus further inhibiting cell contractility and motility. Melatonin actions are most likely attributable to ERK inhibition, although melatonin could display other ERK-independent effects, namely through a direct modulation of additional molecular and structural factors, including Coronin, Cofilin and cytoskeleton components. This article is protected by copyright. All rights reserved.
2018
ERK; ROCK; cofilin; coronin; fascin; melatonin; nicotine; vinculin; extracellular signal-regulated kinase
01 Pubblicazione su rivista::01a Articolo in rivista
Increase in motility and invasiveness of MCF7 cancer cells induced by nicotine is abolished by melatonin through inhibition of ERK phosphorylation / Proietti, Sara; Catizone, Angela; Masiello, Maria Grazia; Dinicola, Simona; Fabrizi, Gianmarco; Minini, Mirko; Ricci, Giulia; Verna, Roberto; Reiter, Russel J; Cucina, Alessandra; Bizzarri, Mariano; Proietti, Catizone UGUALE CONTRIBUTO. - In: JOURNAL OF PINEAL RESEARCH. - ISSN 0742-3098. - STAMPA. - 64:4(2018), pp. 1-17. [10.1111/jpi.12467]
File allegati a questo prodotto
File Dimensione Formato  
Proietti_Increase_2018.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.91 MB
Formato Adobe PDF
1.91 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1079026
Citazioni
  • ???jsp.display-item.citation.pmc??? 19
  • Scopus 36
  • ???jsp.display-item.citation.isi??? 32
social impact