Glucose shortage dependent apoptosis in transformed cells upon activation of UPR-autophagy pathway
Poster
Data di Pubblicazione:
2011
Citazione:
Glucose shortage dependent apoptosis in transformed cells upon activation of UPR-autophagy pathway / A. Monestiroli, C. Balestrieri, D. Gaglio, L. Sala Danna, F. Cammarata, C. Gelfi, L. Alberghina, F. Chiaradonna. - In: THE FEBS JOURNAL. - ISSN 1742-464X. - 278:suppl. 1(2011), pp. 222-222. ((Intervento presentato al 36. convegno FEBS Congress : Biochemistry for Tomorrow's Medicine tenutosi a Torino nel 2011.
Abstract:
The study of cancer metabolism alterations is an expanding area of research aimed to discover novel diagnostic and therapeutic approaches. In this regard, it has been shown that cancer cells use more glucose and accumulate extracellular lactate even in normoxic conditions (Warburg Effect). Accordingly, transformed cells rely mostly on glycolysis for ATP production as compared to normal cells that use mainly OXPHOS. Taking advantage of a cellular model of transformation, the NIH-3T3 murine fibroblasts harboring an oncogenic k-ras gene, we have previously shown that these transformed cells, grown in low glucose availability (1mM), reduce their proliferation and increase cell death as compared to parental cells, NIH-3T3. In order to identify the mechanisms involved in transformed cells apoptosis, a transcriptional analysis of normal and transformed cells grown in optimal glucose availability (25mM) as compared to glucose shortage (1mM) has been performed. The results indicate that both cell lines, when seeded in low glucose, activate genes associated to the Unfolded Protein Response (UPR) and to autophagy. Activation of these processes has been confirmed by protein expression analysis and using chemical modulators of both pathways. Notably, latter experiments have shown that the fate of transformed cells upon glucose shortage is modulated by either UPR or autophagy. Since the autophagic process is strictly linked to UPR, these results highlight the role of UPR-autophagy pathway in the induction of glucose-dependent apoptosis in transformed cells. The full elucidation of this response will help to clarify the role of cancer metabolism in the setting of tumor progression and survival.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
A. Monestiroli, C. Balestrieri, D. Gaglio, L. Sala Danna, F. Cammarata, C. Gelfi, L. Alberghina, F. Chiaradonna
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