title: Combined phosphoproteomics and bioinformatics strategy in deciphering drug resistant related pathways in triple negative breast cancer.
abstract: Because of the absence of a clear therapeutic target for triple negative breast cancer (TNBC), conventional chemotherapy is the only available systemic treatment option for these patients. Despite chemotherapy treatment, TNBC patients still have worse prognosis when compared with other breast cancer patients. The study is to investigate unique phosphorylated proteins expressed in chemoresistant TNBC cell lines. In the current study, twelve TNBC cell lines were subjected to drug sensitivity assays against chemotherapy drugs docetaxel, doxorubicin, gemcitabine, and cisplatin. Based on their half maximal inhibitory concentrations, four resistant and two sensitive cell lines were selected for further analysis. The phosphopeptides from these cells were enriched with TiO2 beads and fractionated using strong cation exchange. 1,645 phosphoprotein groups and 9,585 unique phosphopeptides were identified by a high throughput LC-MS/MS system LTQ-Orbitrap. The phosphopeptides were further filtered with Ascore system and 1,340 phosphoprotein groups, 2,760 unique phosphopeptides, and 4,549 unique phosphosites were identified. Our study suggested that differentially phosphorylated Cdk5, PML, AP-1, and HSF-1 might work together to promote vimentin induced epithelial to mesenchymal transition (EMT) in the drug resistant cells. EGFR and HGF were also shown to be involved in this process.
authors.affiliation: Gonda/UCLA Breast Cancer Research Laboratory and the Revlon/UCLA Breast Center, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 200 Med Plaza, Ste B265-1, Los Angeles, CA 90095-7028, USA.
authors.forename: Xinyu
authors.identifier: 0000-0002-3615-7371
authors.initials: X
authors.lastname: Deng
authors.affiliation: Gonda/UCLA Breast Cancer Research Laboratory and the Revlon/UCLA Breast Center, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 200 Med Plaza, Ste B265-1, Los Angeles, CA 90095-7028, USA.
authors.forename: Morris
authors.identifier: 0000-0002-2150-9864
authors.initials: M
authors.lastname: Kohanfars
authors.affiliation: Gonda/UCLA Breast Cancer Research Laboratory and the Revlon/UCLA Breast Center, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 200 Med Plaza, Ste B265-1, Los Angeles, CA 90095-7028, USA.
authors.forename: Huan Ming
authors.initials: HM
authors.lastname: Hsu
authors.affiliation: The Pasarow Mass Spectrometry Laboratory, NPI-Semel Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Puneet
authors.initials: P
authors.lastname: Souda
authors.affiliation: The Pasarow Mass Spectrometry Laboratory, NPI-Semel Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Capri
authors.affiliation: The Pasarow Mass Spectrometry Laboratory, NPI-Semel Institute, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Whitelegge
authors.affiliation: Gonda/UCLA Breast Cancer Research Laboratory and the Revlon/UCLA Breast Center, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 200 Med Plaza, Ste B265-1, Los Angeles, CA 90095-7028, USA.
authors.forename: Helena R
authors.initials: HR
authors.lastname: Chang