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 (IC 50 =18 mM). In summary, these data suggest that Cav-1 is required for metformin action in NSCLC cells.—Salani, B., Maffioli, S., Hamoudane, M., Parodi, A., Ravera, S., Passalacqua, M., Alama, A., Nhiri, M., Cordera, R., Maggi, D. Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells. NSCLC AKT FOXO3a OCT1 Footnotes This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Received July 8, 2011. Accepted October 20, 2011. © FASEB Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print October 28, 2011 , doi: 10.1096/fj.11-192088 February 2012 The FASEB Journal vol. 26 no. 2 788-798 » Abstract Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.11-192088v1 26/2/788 most recent Classifications Research Communications Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Salani, B. Articles by Maggi, D. PubMed PubMed citation Articles by Salani, B. Articles by Maggi, D. Related Content Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Current Issue February 2012, 26 (2) Alert me to new issues of The FASEB Journal Submit Manuscripts Online Press Room Information for Authors Information for Reviewers Editorial Board Editorial Policies Subscriptions Librarian's Resource Activate Online View Collected Papers Breakthroughs in Bioscience Advertising Copyright Permissions Feedback Subscribe to RSS FASEB Publication Services Go to FASEB Online Copyright © 2012 by the Federation of American Societies for Experimental Biology Print ISSN: 0892-6638 Online ISSN: 1530-6860 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-23107677-1"); pageTracker._trackPageview();

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