title: Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.
abstract: BACKGROUND
  Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood.
  
  
  RESULTS
  Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from "obese" adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses.
  
  
  CONCLUSIONS
  These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression.
authors.affiliation: Discipline of Physiology, School of Medical Sciences & Bosch Institute, The Hub (D17), Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Seher
authors.initials: S
authors.lastname: Balaban
authors.affiliation: Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Shearer
authors.affiliation: Discipline of Physiology, School of Medical Sciences & Bosch Institute, The Hub (D17), Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Lee
authors.affiliation: Centenary Institute, The University of Sydney, Camperdown, NSW 2050 Australia ; Sydney Medical School, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: van Geldermalsen
authors.affiliation: Discipline of Physiology, School of Medical Sciences & Bosch Institute, The Hub (D17), Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia ; Faculty of Medicine, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Schreuder
authors.affiliation: Discipline of Physiology, School of Medical Sciences & Bosch Institute, The Hub (D17), Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Harrison C
authors.initials: HC
authors.lastname: Shtein
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Rose
authors.initials: R
authors.lastname: Cairns
authors.affiliation: School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Kristen C
authors.initials: KC
authors.lastname: Thomas
authors.affiliation: School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fazakerley
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grewal
authors.affiliation: Centenary Institute, The University of Sydney, Camperdown, NSW 2050 Australia ; Sydney Medical School, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Jeff
authors.initials: J
authors.lastname: Holst
authors.affiliation: Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia ; School of Medical Sciences, UNSW Australia, Sydney, NSW 2052 Australia.
authors.forename: Darren N
authors.initials: DN
authors.lastname: Saunders
authors.affiliation: Discipline of Physiology, School of Medical Sciences & Bosch Institute, The Hub (D17), Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hoy
keywords: Adipocytes; Breast cancer; Lipid metabolism; Metabolic crosstalk; Obesity