System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis

Yair Pozniak, Nora Balint-Lahat, Jan Daniel Rudolph, Cecilia Lindskog, Rotem Katzir, Camilla Avivi, Fredrik Pontén, Eytan Ruppin, Iris Barshack, Tamar Geiger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)172-184
Number of pages13
JournalCell Systems
Volume2
Issue number3
DOIs
StatePublished - 23 Mar 2016

Funding

FundersFunder number
Gene Regulation in Complex Human Disease Center41/11
Israeli Center of Research Excellence program
Israel Cancer Research Fund
Israel Science Foundation1617/12

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