title: TPD52 expression increases neutral lipid storage within cultured cells.
abstract: Tumor protein D52 (TPD52) is amplified and/or overexpressed in cancers of diverse cellular origins. Altered cellular metabolism (including lipogenesis) is a hallmark of cancer development, and protein-protein associations between TPD52 and known regulators of lipid storage, and differential TPD52 expression in obese versus non-obese adipose tissue, suggest that TPD52 might regulate cellular lipid metabolism. We found increased lipid droplet numbers in BALB/c 3T3 cell lines stably expressing TPD52, compared with control and TPD52L1-expressing cell lines. TPD52-expressing 3T3 cells showed increased fatty acid storage in triglyceride (from both de novo synthesis and uptake) and formed greater numbers of lipid droplets upon oleic acid supplementation than control cells. TPD52 colocalised with Golgi, but not endoplasmic reticulum (ER), markers and also showed partial colocalisation with lipid droplets coated with ADRP (also known as PLIN2), with a proportion of TPD52 being detected in the lipid droplet fraction. Direct interactions between ADRP and TPD52, but not TPD52L1, were demonstrated using the yeast two-hybrid system, with ADRP-TPD52 interactions confirmed using GST pulldown assays. Our findings uncover a new isoform-specific role for TPD52 in promoting intracellular lipid storage, which might be relevant to TPD52 overexpression in cancer.
authors.affiliation: Molecular Oncology Laboratory, Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia.
authors.forename: Alvin
authors.initials: A
authors.lastname: Kamili
authors.affiliation: Molecular Oncology Laboratory, Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia Discipline of Paediatrics and Child Health, University of Sydney, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia.
authors.forename: Nuruliza
authors.initials: N
authors.lastname: Roslan
authors.affiliation: Molecular Oncology Laboratory, Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia Discipline of Paediatrics and Child Health, University of Sydney, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Frost
authors.affiliation: Discipline of Paediatrics and Child Health, University of Sydney, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia Kids Research Institute Microscope Facility, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia.
authors.forename: Laurence C
authors.initials: LC
authors.lastname: Cantrill
authors.affiliation: Kids Research Institute Microscope Facility, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Molecular Oncology Laboratory, Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia Discipline of Paediatrics and Child Health, University of Sydney, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia.
authors.forename: Austin
authors.initials: A
authors.lastname: Della-Franca
authors.affiliation: Department of Immunology and Molecular Microbiology and TTUHSC Cancer Center, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Bright
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Groblewski
authors.affiliation: Department of General Pathology, Institute of Pathology, Heidelberg 69120, Germany.
authors.forename: Beate K
authors.initials: BK
authors.lastname: Straub
authors.affiliation: Discipline of Physiology, School of Medical Sciences and Bosch Institute and Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hoy
authors.affiliation: Molecular Oncology Laboratory, Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia Discipline of Paediatrics and Child Health, University of Sydney, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia yuyan.chen@health.nsw.gov.au jennifer.byrne@health.nsw.gov.au.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Molecular Oncology Laboratory, Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia Discipline of Paediatrics and Child Health, University of Sydney, The Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia yuyan.chen@health.nsw.gov.au jennifer.byrne@health.nsw.gov.au.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Byrne
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D000070780:Perilipin-2; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D020033:Protein Isoforms; C114751:TPD52 protein, human; C486415:Tpd52 protein, mouse; D014280:Triglycerides
keywords: Golgi; Lipid droplet; Lipid storage; PAT proteins; Tumor protein D52