The Proteomic Landscape of Triple-Negative Breast Cancer

Abstract

SUMMARY Triple-negative breast cancer is a heterogeneous disease characterized by poor clinical outcomes and a shortage of targeted treatment options. To discover molecular features of triple-negative breast cancer, we performed quantitative proteomics analysis of twenty human-derived breast cell lines and four primary breast tumors to a depth of more than 12,000 distinct proteins. We used this data to identify breast cancer subtypes at the protein level and demonstrate the precise quantification of biomarkers, signaling proteins, and biological pathways by mass spectrometry. We integrated proteomics data with exome sequence resources to identify genomic aberrations that affect protein expression. We performed a high-throughput drug screen to identify protein markers of drug sensitivity and understand the mechanisms of drug resistance. The genome and proteome provide complementary information that, when combined, provide a powerful engine for therapeutic discovery. This resource is available to the cancer research community to catalyze further analysis and investigation.

Mitochondrial ribosomes in cancer

“…The identification of novel mutations, epigenetic dysregulation, and aberrant gene expression or protein abundance patterns has yielded deep insights into specific cancer pathogeneses [15, 107, 108]. Genetic, genomic and proteomic variations may serve as markers for diagnostics and in some cases, when a causal relationship is established, as therapeutic targets as well.…”

Studying Interrelation of PDLIM4 with the Model of CD74-Mediated Development of Breast Cancer

“…Even within separate subtypes of BC, it is possible to distinguish the lines that are PDLIM4-positive and PDLIM4-negative (Kravchenko et al, 2015;Lawrence et al, 2015). These results allow to assume the existence of an alternative molecular mechanisms of tumor development, which are associated with suppression or overexpression of PDLIM4, which indicates PDLIM4's ability to act both as an oncosuppressor and an oncogene, depending on the type of the tumor.…”

“…Within the described model, PDLIM4 shows oncogenic properties and turns out to be associated with the most negative cancer forecast. The provided data makes it possible to explain why for several most malignant lines of BC, such as MDA-MB-231, MDA-MB-438 or HCC38, the high level of PDLIM4 expressionism is characteristic (Lawrence et al, 2015).…”

Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity

“…Multiple studies have explored genomic and transcriptomic markers for drug sensitivity in cancer cell lines 1, 3 , but data on the proteome remain limited 11 . Our comparison of omics modalities for the identification of known drug-target gene or pathway relationships in CRC cell lines demonstrates the potential of global proteomic data to predict therapeutic responses.…”

“…Genomic analyses indicate that established cancer cell lines are suitable molecular proxies for primary tumors in many cancer types 2 , yet findings at the transcriptomic level have been variable, with data for hepatocellular carcinoma 8 and colorectal cancer (CRC) 9 indicating similarity between cell lines and primary tumors, whilst data for breast cancer suggest pronounced differences 10 . Although some global proteomics data sets for cancer cell lines are available 11, 12 there exists no large-scale proteomic study comparing cell lines with primary tumors. It remains unknown whether cancer cell lines are representative of primary tumors at the proteome level and to what extent molecular programs and proteogenomic relationships are maintained in vitro .…”