Phosphoproteomic analysis identifies FAK2 as a potential therapeutic target for tamoxifen resistance in breast cancer.

Phosphoproteomic analysis identifies FAK2 as a potential therapeutic target for tamoxifen resistance in breast cancer. Mol Cell Proteomics. 2015 Sep 1; Authors: Wu X, Zahari MS, Renuse S, Nirujogi RS, Kim MS, Manda SS, Stearns V, Gabrielson E, Sukumar S, Pandey A Abstract Tamoxifen, an estrogen receptor-α (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5,600 unique phosphopeptides identified, 1,529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was the most enriched signaling pathway activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally upregulated in tamoxifen resistant cells. FAK2 sup...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research