PMID- 22038047
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20220321
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 26
IP  - 2
DP  - 2012 Feb
TI  - Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in 
      non-small-cell lung cancer cells.
PG  - 788-98
LID - 10.1096/fj.11-192088 [doi]
AB  - 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.
FAU - Salani, Barbara
AU  - Salani B
AD  - Department of Endocrinology and Medicine, University of Genoa, Genoa, Italy.
FAU - Maffioli, Sara
AU  - Maffioli S
FAU - Hamoudane, Meriem
AU  - Hamoudane M
FAU - Parodi, Alessia
AU  - Parodi A
FAU - Ravera, Silvia
AU  - Ravera S
FAU - Passalacqua, Mario
AU  - Passalacqua M
FAU - Alama, Angela
AU  - Alama A
FAU - Nhiri, Mohamed
AU  - Nhiri M
FAU - Cordera, Renzo
AU  - Cordera R
FAU - Maggi, Davide
AU  - Maggi D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111028
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (CAV1 protein, human)
RN  - 0 (Caveolin 1)
RN  - 0 (FOXO3 protein, human)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (RNA, Small Interfering)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Base Sequence
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/*metabolism/pathology
MH  - Caveolin 1/antagonists & inhibitors/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology
MH  - Insulin-Like Growth Factor I/*antagonists & inhibitors
MH  - Lung Neoplasms/*drug therapy/genetics/*metabolism/pathology
MH  - Metformin/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Receptor, IGF Type 1/metabolism
MH  - Signal Transduction/drug effects
EDAT- 2011/11/01 06:00
MHDA- 2012/04/10 06:00
CRDT- 2011/11/01 06:00
PHST- 2011/11/01 06:00 [entrez]
PHST- 2011/11/01 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
AID - fj.11-192088 [pii]
AID - 10.1096/fj.11-192088 [doi]
PST - ppublish
SO  - FASEB J. 2012 Feb;26(2):788-98. doi: 10.1096/fj.11-192088. Epub 2011 Oct 28.