BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is the Elongation Factor EF1alpha. EF1alpha contains a putative Akt phosphorylation site, but is not phosphorylated by pAkt1 or pAkt2, suggesting that it may function as a modulator of pAkt activity. Indeed, downregulation of EF1alpha expression by siRNAs led to markedly decreased expression of pAkt1 and to less extent of pAkt2 and was associated with reduced proliferation, survival and invasion of HCC1937 cells. Proliferation and survival was further reduced by combining EF1alpha siRNAs with specific pAkt inhibitors whereas EF1alpha downregulation slightly attenuated the decreased invasion induced by Akt inhibitors. CONCLUSION: We show here that EF1alpha is a pAkt-interacting protein which regulates pAkt levels. Since EF1alpha is often overexpressed in breast cancer, the consequences of EF1alpha increased levels for proliferation, survival and invasion will likely depend on the relative concentration of Akt1 and Akt2.

Elongation factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility / Pecorari, Luisa; Marin, O.; Silvestri, C.; Candini, Olivia; Rossi, Elena; Guerzoni, Clara; Cattelani, Sara; Mariani, S. A.; Corradini, Francesca; Ferrari, Giovanna; Cortesi, L.; Bussolari, Rita; Raschellà, G.; Federico, Massimo; Calabretta, Bruno. - In: MOLECULAR CANCER. - ISSN 1476-4598. - STAMPA. - 8(2009), pp. 58-69. [10.1186/1476-4598-8-58]

Elongation factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility

PECORARI, Luisa;CANDINI, Olivia;ROSSI, Elena;GUERZONI, Clara;CATTELANI, Sara;CORRADINI, Francesca;FERRARI, Giovanna;BUSSOLARI, Rita;FEDERICO, Massimo;CALABRETTA, Bruno
2009

Abstract

BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is the Elongation Factor EF1alpha. EF1alpha contains a putative Akt phosphorylation site, but is not phosphorylated by pAkt1 or pAkt2, suggesting that it may function as a modulator of pAkt activity. Indeed, downregulation of EF1alpha expression by siRNAs led to markedly decreased expression of pAkt1 and to less extent of pAkt2 and was associated with reduced proliferation, survival and invasion of HCC1937 cells. Proliferation and survival was further reduced by combining EF1alpha siRNAs with specific pAkt inhibitors whereas EF1alpha downregulation slightly attenuated the decreased invasion induced by Akt inhibitors. CONCLUSION: We show here that EF1alpha is a pAkt-interacting protein which regulates pAkt levels. Since EF1alpha is often overexpressed in breast cancer, the consequences of EF1alpha increased levels for proliferation, survival and invasion will likely depend on the relative concentration of Akt1 and Akt2.
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58
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Elongation factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility / Pecorari, Luisa; Marin, O.; Silvestri, C.; Candini, Olivia; Rossi, Elena; Guerzoni, Clara; Cattelani, Sara; Mariani, S. A.; Corradini, Francesca; Ferrari, Giovanna; Cortesi, L.; Bussolari, Rita; Raschellà, G.; Federico, Massimo; Calabretta, Bruno. - In: MOLECULAR CANCER. - ISSN 1476-4598. - STAMPA. - 8(2009), pp. 58-69. [10.1186/1476-4598-8-58]
Pecorari, Luisa; Marin, O.; Silvestri, C.; Candini, Olivia; Rossi, Elena; Guerzoni, Clara; Cattelani, Sara; Mariani, S. A.; Corradini, Francesca; Ferrari, Giovanna; Cortesi, L.; Bussolari, Rita; Raschellà, G.; Federico, Massimo; Calabretta, Bruno
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/622927
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