Moonlighting Proteins and Cardiopathy in the Spatial Response of MCF‐7 Breast Cancer Cells to Tamoxifen

Abstract

BackgroundThe purpose of this study is to apply quantitative high‐throughput proteomics methods to investigate dynamic aspects of protein changes in nucleocytoplasmic distribution of proteins and of total protein abundance for MCF‐7 cells exposed to tamoxifen (Tam) in order to reveal the agonistic and antagonistic roles of the drug.Experimental designThe MS‐based global quantitative proteomics with the analysis of fractions enriched in target subcellular locations is applied to measure the changes in total abundance and in the compartmental abundance/distribution between the nucleus and cytoplasm for several thousand proteins differentially expressed in MCF‐7 cells in response to Tam stimulation.ResultsThe response of MCF‐7 cells to the Tam treatment shows significant changes in subcellular abundance rather than in their total abundance. The bioinformatics study reveals the relevance of moonlighting proteins and numerous pathways involved in Tam response of MCF‐7 including some of which may explain the agonistic and antagonistic roles of the drug.ConclusionsThe results indicate possible protective role of Tam against cardiovascular diseases as well as its involvement in G‐protein coupled receptors pathways that enhance breast tissue proliferation.

A proteomic landscape of pharmacologic perturbations for functional relevance

“…(B) The in-vitro validation of the 20S proteasome inhibition. The prediction used signatures from the published proteome data [ 37 ]. (C) The pharmacological activities of CC-885 (25 nM) (left) and statin drugs (right) in HCT116 cell line.…”

“…Tamoxifen and 4-hydroxytamoxifen, which are selective estrogen receptor modulators, have been used clinically to treat patients with ER-positive breast cancer [ 36 ]. We extracted the proteomic signature of 4-hydroxytamoxifen ( Table S5 ) in a previous study [ 37 ] and used this signature for database “query” process. Surprisingly, we found that the proteomic fingerprints of 4-hydroxytamoxifen presented potentially diverse pharmacological activities, such as an AMPK activator (metformin), a proteasome inhibitor (carfilzomib), an Mdm2 inhibitor (Nutlin-3a), and an epigenetic inhibitor (valproic acid and JQ-1).…”