Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response. (Articolo in rivista) (literal)

Anno

• 2013-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1038/cddis.2013.257 (literal)

Alternative label

• R Palorini 1,2; Francesco Cammarata 3; C Balestrieri 2,6; A Monestiroli 2; Michele Vasso 4; Cecilia Gelfi 1,4,5; Lilia Alberghina 1,2; F Chiaradonna 1,2. (2013)
  Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response.
  in Cell death and disease
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• R Palorini 1,2; Francesco Cammarata 3; C Balestrieri 2,6; A Monestiroli 2; Michele Vasso 4; Cecilia Gelfi 1,4,5; Lilia Alberghina 1,2; F Chiaradonna 1,2. (literal)

Pagina inizio

• e732 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni

• Corrigendum: Cell Death Dis, 2013; 4: e910. Correction to: Cell Death and Disease (2013) 4, e732; doi:10.1038/cddis.2013.257; published online 18 July 2013 Since the publication of this article, the authors have noticed that Francesco Paolo Cammarata's name was incorrect. The correct author list is shown above. The corrected article appears online together with this corrigendum. The authors would like to apologize for any inconvenience. (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 4 (literal)

Rivista

• Cell death and disease (Rivista)

Note

• PubMe (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• 1. SYSBIO, Centre of Systems Biology Milano, Italy 2. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy. 3. LATO-HSR G.Giglio, Cefalù (PA), Italy. 4. Institute of Bioimaging and Molecular Physiology, National Research Council, Segrate (MI), Italy. 5. Department of Biomedical Sciences for Health, University of Milan, Segrate (MI) Italy. (literal)

Titolo

• Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response. (literal)

Abstract

• Cancer cells, which use more glucose than normal cells and accumulate extracellular lactate even under normoxic conditions (Warburg effect), have been reported to undergo cell death under glucose deprivation, whereas normal cells remain viable. As it may be relevant to exploit the molecular mechanisms underlying this biological response to achieve new cancer therapies, in this paper we sought to identify them by using transcriptome and proteome analysis applied to an established glucose-addicted cellular model of transformation, namely, murine NIH-3T3 fibroblasts harboring an oncogenic K-RAS gene, compared with parental cells. Noteworthy is that the analyses performed in high- and low-glucose cultures indicate that reduction of glucose availability induces, especially in transformed cells, a significant increase in the expression of several unfolded protein response (UPR) hallmark genes. We show that this response is strictly associated with transformed cell death, given that its attenuation, by reducing protein translation or by increasing cell protein folding capacity, preserves the survival of transformed cells. Such an effect is also observed by inhibiting c-Jun NH2-terminal kinase, a pro-apoptotic signaling mediator set downstream of UPR. Strikingly, addition of N-acetyl-D-glucosamine, a specific substrate for the hexosamine biosynthesis pathway (HBP), to glucose-depleted cells completely prevents transformed cell death, stressing the important role of glucose in HBP fuelling to ensure UPR attenuation and increased cell survival. Interestingly, these results have been fully recognized in a human model of breast cancer, MDA-MB-231 cells. In conclusion, we show that glucose deprivation, leading to harmful accumulation of unfolded proteins in consequence of a reduction of protein glycosylation, induces a UPR-dependent cell death mechanism. These findings may open the way for new therapeutic strategies to specifically kill glycolytic cancer cells. (literal)

Prodotto di

• Proteomica differenziale di tessuti patologici e fluidi biologici per la comprensione della biologia dei sistemi (ME.P06.026.002) (Modulo)
• Institute of molecular bioimaging and physiology (IBFM) (Istituto)

Autore CNR

• CECILIA GELFI (Unità di personale esterno)
• MICHELE VASSO (Unità di personale interno)
• FRANCESCO PAOLO CAMMARATA (Persona)

Insieme di parole chiave

• Parole chiave di "Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response." (Insieme di parole chiave)

Incoming links:

Prodotto

• Institute of molecular bioimaging and physiology (IBFM) (Istituto)
• Proteomica differenziale di tessuti patologici e fluidi biologici per la comprensione della biologia dei sistemi (ME.P06.026.002) (Modulo)

Autore CNR di

• MICHELE VASSO (Unità di personale interno)
• FRANCESCO PAOLO CAMMARATA (Persona)
• CECILIA GELFI (Unità di personale esterno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Cell death and disease (Rivista)

Insieme di parole chiave di

• Parole chiave di "Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response." (Insieme di parole chiave)