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SUMMARY:‘Tracking metabolic reprogramming in cancers with PI3K/Akt activ
 ation’ - George Poulogiannis\, Team Leader\, Division of Cancer Biology\
 , Institute of Cancer Research\, London
DTSTART:20171205T113000Z
DTEND:20171205T123000Z
UID:TALK96058@talks.cam.ac.uk
CONTACT:Mala Jayasundera
DESCRIPTION:The PI3K/Akt pathway represents a complex signalling network t
 hat integrates numerous upstream stimuli to regulate diverse cellular proc
 esses\, including cell growth\, proliferation\, survival\, and migration. 
 Many components of this pathway have been implicated in cancer\, and sever
 al PI3K/Akt/mTOR inhibitors have been tested in clinical trials\, however 
 neither PTEN\, nor PIK3CA mutation status are associated with anti-tumour 
 response in cancer patients with advanced disease. Metabolic reprogramming
  is a hallmark of cancer and just as activation of the PI3K/Akt pathway le
 ads to marked changes in cellular metabolism\, recent data from our group 
 demonstrate that dysregulated metabolism can also affect the activation of
  this pathway. We showed that depletion of PARK2\, a gene encoding the E3 
 Ligase Parkin\, which has a key functional contribution in preserving mito
 chondrial integrity promotes the inhibition of PTEN by S-nitrosylation. No
 tably\, this modification is important in supporting cancer cell survival 
 and proliferation under conditions of energy deprivation. \n\nOur efforts 
 for tracking metabolic reprogramming in cancers with PI3K/Akt activation c
 ontinue with the use of the intelligent Knife (iKnife) coupled to Rapid Ev
 aporative Ionization Mass Spectrometry (REIMS). Gaseous ions present in th
 e plume generated by tissue cauterization may be directly analysed\, provi
 ding highly specific spectroscopic and chemometric processing that allows 
 near-real-time characterisation of lipid metabolism. Our results demonstra
 te that iKnife/REIMS profiling allows a very robust metabolic classificati
 on of breast cancer into two major subtypes (lipogenic and non-lipogenic) 
 with distinctive lipid signatures and overall lipid content. We demonstrat
 e that the lipogenic subtype is highly enriched in PIK3CA mutations\, but 
 not loss or mutation in PTEN and depends predominantly on mTORC2 activatio
 n\, opening up opportunities to investigate the mechanistic basis underlyi
 ng potential metabolic vulnerabilities. \n\n
LOCATION:Sackler Lecture Theatre (Level 7)\, Cambridge Institute for Medic
 al Research
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