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SUMMARY:Metabolic rewiring drives invasion and metastasis in mammary carci
 noma - Jim Norman\, Cancer Research UK Beatson Institute
DTSTART:20211029T120000Z
DTEND:20211029T130000Z
UID:TALK151582@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:The CRUK-Beatson Institute has an ongoing programme to map can
 cer-associated metabolomic landscapes. This has indicated that alterations
  to the serum metabolome presage metastatic onset. In mammary cancers\, el
 evated circulating glutamate is a prominent feature of the metastasis-asso
 ciated metabolome\, and this is owing to upregulated expression of the glu
 tamate-cystine antiporter\, xCT (SLC7A11) in metabolically-stressed cancer
  cells. Extracellular glutamate then activates a metabotropic glutamate re
 ceptor\, mGluR3 to drive invasive behaviour by enlisting membrane traffick
 ing events dependent on the Rab27 GTPase. Consistently\, Rab27a knockout m
 ice bearing autochthonous MMTV-PyMT mammary tumours display reduced metast
 asis to the lungs. Through exploring the cellular mechanisms responsible f
 or this\, we have found that Rab27a participates in a membrane trafficking
  process in which mitochondrial material (including mitochondrial DNA (mtD
 NA)) is packaged into exosomes. mtDNA-containing exosomes are then release
 d from cancer cells to evoke invasive behaviour in neighbouring cells by a
 ctivating a toll-like receptor\, TLR9. Thus\, this work has led us to disc
 over a pathway through which metabolic rewiring in cancers can drive invas
 ion and metastasis by releasing mtDNA-containing exosomes to influence the
  behaviour of other cells in the tumour microenvironment and beyond. 
LOCATION:CRUK CI Lecture Theatre
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