IGF1 regulates PKM2 function through Akt phosphorylation

Barbara Salani, Silvia Ravera, Adriana Amaro, Annalisa Salis, Mario Passalacqua, Enrico Millo, Gianluca Damonte, Cecilia Marini, Ulrich Pfeffer, Gianmario Sambuceti, Renzo Cordera, Davide Maggi

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 languageEnglish
Pages (from-to)1559-1567
Number of pages9
JournalCell Cycle
Volume14
Issue number10
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Pyruvate Kinase
Phosphorylation
Metformin
Glycolysis
Glucose
Biosynthetic Pathways
Intercellular Signaling Peptides and Proteins

Keywords

  • HIF1α
  • IGF1
  • IGFIR
  • PKM2

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Salani, B., Ravera, S., Amaro, A., Salis, A., Passalacqua, M., Millo, E., ... Maggi, D. (2015). IGF1 regulates PKM2 function through Akt phosphorylation. Cell Cycle, 14(10), 1559-1567. https://doi.org/10.1080/15384101.2015.1026490

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 journalArticle

Salani, B, Ravera, S, Amaro, A, Salis, A, Passalacqua, M, Millo, E, Damonte, G, Marini, C, Pfeffer, U, Sambuceti, G, Cordera, R & Maggi, D 2015, 'IGF1 regulates PKM2 function through Akt phosphorylation', Cell Cycle, vol. 14, no. 10, pp. 1559-1567. https://doi.org/10.1080/15384101.2015.1026490
Salani B, Ravera S, Amaro A, Salis A, Passalacqua M, Millo E et al. IGF1 regulates PKM2 function through Akt phosphorylation. Cell Cycle. 2015 Jan 1;14(10):1559-1567. https://doi.org/10.1080/15384101.2015.1026490
Salani, Barbara ; Ravera, Silvia ; Amaro, Adriana ; Salis, Annalisa ; Passalacqua, Mario ; Millo, Enrico ; Damonte, Gianluca ; Marini, Cecilia ; Pfeffer, Ulrich ; Sambuceti, Gianmario ; Cordera, Renzo ; Maggi, Davide. / IGF1 regulates PKM2 function through Akt phosphorylation. In: Cell Cycle. 2015 ; Vol. 14, No. 10. pp. 1559-1567.
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