Abstract
Pyruvate kinase M2 (PKM2) acts at the crossroad of growth and metabolism pathways in cells. PKM2 regulation by growth factors can redirect glycolytic intermediates into key biosynthetic pathway. Here we show that IGF1 can regulate glycolysis rate, stimulate PKM2 Ser/Thr phosphorylation and decrease cellular pyruvate kinase activity. Upon IGF1 treatment we found an increase of the dimeric form of PKM2 and the enrichment of PKM2 in the nucleus. This effect was associated to a reduction of pyruvate kinase enzymatic activity and was reversed using metformin, which decreases Akt phosphorylation. IGF1 induced an increased nuclear localization of PKM2 and STAT3, which correlated with an increased HIF1α, HK2, and GLUT1 expression and glucose entrapment. Metformin inhibited HK2, GLUT1, HIF-1α expression and glucose consumption. These findings suggest a role of IGFIR/Akt axis in regulating glycolysis by Ser/Thr PKM2 phosphorylation in cancer cells.
| Original language | English |
|---|---|
| Pages (from-to) | 1559-1567 |
| Number of pages | 9 |
| Journal | Cell Cycle |
| Volume | 14 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Jan 1 2015 |
Fingerprint
Keywords
- HIF1α
- IGF1
- IGFIR
- PKM2
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Developmental Biology
Cite this
IGF1 regulates PKM2 function through Akt phosphorylation. / Salani, Barbara; Ravera, Silvia; Amaro, Adriana; Salis, Annalisa; Passalacqua, Mario; Millo, Enrico; Damonte, Gianluca; Marini, Cecilia; Pfeffer, Ulrich; Sambuceti, Gianmario; Cordera, Renzo; Maggi, Davide.
In: Cell Cycle, Vol. 14, No. 10, 01.01.2015, p. 1559-1567.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IGF1 regulates PKM2 function through Akt phosphorylation
AU - Salani, Barbara
AU - Ravera, Silvia
AU - Amaro, Adriana
AU - Salis, Annalisa
AU - Passalacqua, Mario
AU - Millo, Enrico
AU - Damonte, Gianluca
AU - Marini, Cecilia
AU - Pfeffer, Ulrich
AU - Sambuceti, Gianmario
AU - Cordera, Renzo
AU - Maggi, Davide
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Pyruvate kinase M2 (PKM2) acts at the crossroad of growth and metabolism pathways in cells. PKM2 regulation by growth factors can redirect glycolytic intermediates into key biosynthetic pathway. Here we show that IGF1 can regulate glycolysis rate, stimulate PKM2 Ser/Thr phosphorylation and decrease cellular pyruvate kinase activity. Upon IGF1 treatment we found an increase of the dimeric form of PKM2 and the enrichment of PKM2 in the nucleus. This effect was associated to a reduction of pyruvate kinase enzymatic activity and was reversed using metformin, which decreases Akt phosphorylation. IGF1 induced an increased nuclear localization of PKM2 and STAT3, which correlated with an increased HIF1α, HK2, and GLUT1 expression and glucose entrapment. Metformin inhibited HK2, GLUT1, HIF-1α expression and glucose consumption. These findings suggest a role of IGFIR/Akt axis in regulating glycolysis by Ser/Thr PKM2 phosphorylation in cancer cells.
AB - Pyruvate kinase M2 (PKM2) acts at the crossroad of growth and metabolism pathways in cells. PKM2 regulation by growth factors can redirect glycolytic intermediates into key biosynthetic pathway. Here we show that IGF1 can regulate glycolysis rate, stimulate PKM2 Ser/Thr phosphorylation and decrease cellular pyruvate kinase activity. Upon IGF1 treatment we found an increase of the dimeric form of PKM2 and the enrichment of PKM2 in the nucleus. This effect was associated to a reduction of pyruvate kinase enzymatic activity and was reversed using metformin, which decreases Akt phosphorylation. IGF1 induced an increased nuclear localization of PKM2 and STAT3, which correlated with an increased HIF1α, HK2, and GLUT1 expression and glucose entrapment. Metformin inhibited HK2, GLUT1, HIF-1α expression and glucose consumption. These findings suggest a role of IGFIR/Akt axis in regulating glycolysis by Ser/Thr PKM2 phosphorylation in cancer cells.
KW - HIF1α
KW - IGF1
KW - IGFIR
KW - PKM2
UR - http://www.scopus.com/inward/record.url?scp=84943803984&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943803984&partnerID=8YFLogxK
U2 - 10.1080/15384101.2015.1026490
DO - 10.1080/15384101.2015.1026490
M3 - Article
AN - SCOPUS:84943803984
VL - 14
SP - 1559
EP - 1567
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 10
ER -