Reference : Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/27275
Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.
English
Palorini, Roberta [> >]
Votta, Giuseppina [> >]
Pirola, Yuri [> >]
De Vitto, Humberto [> >]
De Palma, Sara [> >]
Airoldi, Cristina [> >]
Vasso, Michele [> >]
Ricciardiello, Francesca [> >]
Lombardi, Pietro Paolo [> >]
Cirulli, Claudia [> >]
Rizzi, Raffaella [> >]
Nicotra, Francesco [> >]
Hiller, Karsten mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Gelfi, Cecilia [> >]
Alberghina, Lilia [> >]
Chiaradonna, Ferdinando [> >]
2016
PLoS genetics
12
3
e1005931
Yes (verified by ORBilu)
1553-7390
1553-7404
United States
[en] Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading to their survival and aggressiveness. Although increased resistance to glucose starvation has been shown to be a consequence of signaling pathways and compensatory metabolic routes activation, the full repertoire of the underlying molecular alterations remain elusive. Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA) axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. Notably, here we show that such a PKA-dependent survival is mediated by parallel activation of autophagy and glutamine utilization that in concert concur to attenuate the endoplasmic reticulum (ER) stress and to sustain cell anabolism. Indeed, the inhibition of PKA-mediated autophagy or glutamine metabolism increased the level of cell death, suggesting that the induction of autophagy and metabolic rewiring by PKA is important for cancer cellular survival under glucose starvation. Importantly, both processes actively participate to cancer cell survival mediated by suspension-activated PKA as well. In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment.
Luxembourg Centre for Systems Biomedicine (LCSB): Metabolomics (Hiller Group)
http://hdl.handle.net/10993/27275
10.1371/journal.pgen.1005931

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