Seminar: Tamar Geiger, theme Cancer development and immune defence

System-wide clinical proteomics of breast cancer reveals global remodeling of cellular homeostasis

Date:
23 September 2015 09:30 hrs. - 10:30 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
System-wide clinical proteomics of breast cancer reveals global remodeling of cellular homeostasis
Speaker(s):

Tamar Geiger, Tel Aviv University, Israel 

Host(s):

Michiel Vermeulen & Nina Hubner, Dept. of Molecular Biology, RIMLS

23-09-2015 09:30:0023-09-2015 10:30:00Europe/AmsterdamSystem-wide clinical proteomics of breast cancer reveals global remodeling of cellular homeostasis Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

undefinedThe genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. In recent years, developments in mass spectrometric technology, sample preparation techniques and computational analysis opened new possibilities for genome-scale proteomic analysis of clinical samples. We used the recently developed super-SILAC mix, which is a mixture of lysates of five SILAC-labeled cell lines that serves as an internal standard for accurate tissue quantification. Combined with high-resolution, high-accuracy mass spectrometry we performed a deep analysis of breast cancer progression using clinical breast samples from lymph node negative and lymph node positive luminal tumors, as well as matched lymph node metastases and healthy breast epithelia. We quantified over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways that regulate tumorigenesis and metastatic spread. Surprisingly, we found an anti-Warburg effect dominating the metabolic changes, in which the cancer cells show higher oxidative phosphorylation and lower glycolytic activity. In addition, we extracted a 65-protein signature that predicts lymph node involvement based solely on the primary tumor, which may hold important clinical significance in disease management and treatment.

Key publications

  • Proteomic portrait of human breast cancer progression identifies novel prognostic markers. Cancer Res.; 72:2428-39, 2012. 
  • Metabolic associations of reduced proliferation and oxidative stress in advanced breast cancer. Cancer Res.; 72:5712-20, 2012.
  • Super-SILAC mix for quantitative proteomics of human tumor tissue. Nat Methods; 7:383-5, 2010.  


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