Yair Pozniak,1 Nora Balint-Lahat,2 Jan Daniel Rudolph,1,3 Cecilia Lindskog,4 Rotem Katzir,5 Camilla Avivi,2 Fredrik Ponte´ n,4 Eytan Ruppin,3,5,6 Iris Barshack,2,7,8 and Tamar Geiger1,8,*
Cell Systems 2, 172 – 184, 2016
The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures.
1Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel 2Institute of Pathology, Sheba Medical Center, Tel Hashomer 5265601, Israel 3School of Computer Sciences, Tel Aviv University, Tel Aviv 6997801, Israel 4Department of Immunology Genetics and Pathology, Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden 5Department of Computer Science & Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA 6Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel 7Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel 8Co-senior author