Poster Presentation 2nd Australian Cancer and Metabolism Meeting 2017

Dynamic association of Tumor protein D52 with lipid droplets and the Golgi apparatus (#49)

Yuyan Chen 1 2 , Sarah Frost 1 2 , Matloob Khushi 3 , Laurence Cantrill 2 4 , Hong Yu 5 , Jonathan Arthur 3 , Robert Bright 6 , Guy Groblewski 7 , Jennifer Byrne 1 2
  1. Kids Research Institute, The Children's Hospital at Westmead, Westmead, NSW, Australia
  2. Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia
  3. Bioinformatics Unit, Children’s Medical Research Institute, Sydney, NSW, Australia
  4. Kids Research Institute Microscope Facility, The Children’s Hospital at Westmead, Sydney, NSW, Australia
  5. Microscope Facility, Westmead Institute for Medical Research, Sydney, NSW, Australia
  6. Department of Immunology and Molecular Microbiology and TTUHSC Cancer Center, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
  7. Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin, USA

Altered cellular metabolism (including lipogenesis) is a hallmark of cancer development. Our group has previously found that expression of Tumor Protein D52 (TPD52), which is amplified/ overexpressed in cancers of diverse cellular origins, increases neutral lipid storage within cultured cells (1). TPD52 co-localised with Golgi but not ER markers, and also showed partial co-localisation with Adrp-coated lipid droplets (LDs). As Brefeldin A (BFA) treatment alters both Golgi structure and lipid storage, we examined BFA effects in TPD52-expressing 3T3 cells, and in human AU-565 and HMC-1-8 breast cancer cells, all of which contain prominent LDs. Five-hour BFA treatment reduced median LD numbers in TPD52-expressing 3T3 cells, but increased LD areas. TPD52 knock-down also decreased both LD areas and numbers, and blunted BFA’s effects on LD numbers per cell. In TPD52-expressing 3T3 cells treated with BFA for 1-3 hours, TPD52 co-localised with the trans-Golgi network protein syntaxin 6. However, after 4-5 hours of BFA treatment, TPD52 showed significantly increased co-localisation with LDs in each cell line. Four hours of BFA treatment also increased Tip47 but reduced Adrp detection at LDs in TPD52-expressing 3T3 cells, with Tip47 recruitment to LDs preceding that of TPD52. LD co-localisation of TPD52 but not Tip47 was disrupted by nocodazole when co-treated with BFA. TPD52 may therefore participate in a temporal hierarchy of proteins that respond to alterations in lipid storage, with TPD52 recruitment to LDs being delayed relative to other LD regulators.

 

Reference:

  1. Kamili A, Roslan N, Frost S, Cantrill LC, Wang D, Della-Franca A, et al. TPD52 expression increases neutral lipid storage within cultured cells. J Cell Sci. 2015;128(17):3223-38.