Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells

Barbara Salani, Sara Maffioli, Meriem Hamoudane, Alessia Parodi, Silvia Ravera, Mario Passalacqua, Angela Alama, Mohamed Nhiri, Renzo Cordera, Davide Maggi

Research output: Contribution to journalArticle

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Abstract

Metformin causes an AMP/ATP ratio increase and AMP-activated protein kinase (AMPK) activation. Since caveolin-1 (Cav-1) plays a role in AMPK activation and energy balance, we investigated whether Cav-1 could participate in metformin's inhibitory effect on IGF1 signaling. The effect of metformin was studied in two non-small-cell lung cancer (NSCLC) cell lines, Calu-1 and Calu-6, expressing higher and lower amounts of Cav-1, respectively. In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation. Here, we show that sensitivity of NSCLC cells to metformin was dependent on Cav-1 expression and that metformin required Cav-1 to induce AMPK phosphorylation and AMP/ATP ratio increase. Cav-1 silencing in Calu-1 and overexpression in Calu-6 reduced and improved, respectively, the inhibitory effect of metformin on IGF1-dependent Akt phosphorylation. Prolonged metformin treatment in Calu-6 cells induced a dose-dependent expression increase of Cav-1 and OCT1, a metformin transporter. Cav-1 and OCT1 expression was associated with the antiproliferative effect of metformin in Calu-6 cells (IC50=18 mM). In summary, these data suggest that Cav-1 is required for metformin action in NSCLC cells.

Original languageEnglish
Pages (from-to)788-798
Number of pages11
JournalFASEB Journal
Volume26
Issue number2
DOIs
Publication statusPublished - Feb 2012

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Caveolin 1
Metformin
Non-Small Cell Lung Carcinoma
Cells
Phosphorylation
AMP-Activated Protein Kinases
Adenosine Monophosphate
Adenosine Triphosphate
Chemical activation
Forkhead Transcription Factors
IGF Type 1 Receptor
Cell proliferation
Energy balance
Inhibitory Concentration 50
Cell Proliferation

Keywords

  • AKT
  • FOXO3a
  • NSCLC
  • OCT1

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Salani, B., Maffioli, S., Hamoudane, M., Parodi, A., Ravera, S., Passalacqua, M., ... Maggi, D. (2012). Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells. FASEB Journal, 26(2), 788-798. https://doi.org/10.1096/fj.11-192088

Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells. / Salani, Barbara; Maffioli, Sara; Hamoudane, Meriem; Parodi, Alessia; Ravera, Silvia; Passalacqua, Mario; Alama, Angela; Nhiri, Mohamed; Cordera, Renzo; Maggi, Davide.

In: FASEB Journal, Vol. 26, No. 2, 02.2012, p. 788-798.

Research output: Contribution to journalArticle

Salani, B, Maffioli, S, Hamoudane, M, Parodi, A, Ravera, S, Passalacqua, M, Alama, A, Nhiri, M, Cordera, R & Maggi, D 2012, 'Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells', FASEB Journal, vol. 26, no. 2, pp. 788-798. https://doi.org/10.1096/fj.11-192088
Salani B, Maffioli S, Hamoudane M, Parodi A, Ravera S, Passalacqua M et al. Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells. FASEB Journal. 2012 Feb;26(2):788-798. https://doi.org/10.1096/fj.11-192088
Salani, Barbara ; Maffioli, Sara ; Hamoudane, Meriem ; Parodi, Alessia ; Ravera, Silvia ; Passalacqua, Mario ; Alama, Angela ; Nhiri, Mohamed ; Cordera, Renzo ; Maggi, Davide. / Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells. In: FASEB Journal. 2012 ; Vol. 26, No. 2. pp. 788-798.
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