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Published on: September 19, 2018
Proteomic analysis of talazoparib resistance in triple-negative breast cancer cells
Gamze Guney Eskiler1, Sevinc Yanar2, Gurler Akpinar2
1Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.
Abstract:
Talazoparib (TAL) has been effectively used for the treatment of gBRCA1/2-mutated HER2-negative metastatic breast cancer. However, acquired resistance to TAL remains a major challenge that impedes the clinical success of TAL treatment. Therefore, elucidation of proteins and pathways that contribute to or are affected by the TAL resistance is urgently needed to improve the treatment response and provide novel treatment strategies for advanced metastatic breast cancers. Herein, we aimed to investigate the altered protein signatures in TAL-resistant triple-negative breast cancer (TNBC) cells by comparing with the TNBC parental cell line via proteomic analysis. After validation of TAL-resistance by WST-1 and Annexin V analysis, two-dimensional gel electrophoresis (2DE)-based proteomic analysis coupled to matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF) mass spectrometry was performed to identify differentially regulated proteins. The findings revealed the identities of 10 differentially regulated proteins in TAL-resistant TNBC cells whose bioinformatic analysis predicted changes in EGF/FGF signaling pathways as well as in the AMPK signaling pathway. In addition, phosphorylation/dephosphorylation dynamics were predicted to be altered in TAL-resistant cells. The proteins identified in this study might be the targets to overcome TAL resistance for the treatment of TNBC.
Insights
Acquired resistance to talazoparib (TAL) in breast cancer is a challenge. Proteomic analysis identified 10 proteins and altered signaling pathways in resistant cells, offering potential targets to overcome talazoparib resistance.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Talazoparib (TAL) is effective for gBRCA1/2-mutated HER2-negative metastatic breast cancer.
- Acquired resistance to TAL limits its clinical efficacy, necessitating research into resistance mechanisms.
- Understanding TAL resistance is crucial for developing improved treatment strategies for advanced breast cancers.
Purpose of the Study:
- To investigate altered protein signatures in TAL-resistant triple-negative breast cancer (TNBC) cells.
- To identify potential therapeutic targets for overcoming TAL resistance in TNBC.
- To compare proteomic profiles of TAL-resistant TNBC cells with their parental counterparts.
Main Methods:
- Proteomic analysis using two-dimensional gel electrophoresis (2DE) coupled with MALDI-TOF mass spectrometry.
- Validation of TAL resistance using WST-1 and Annexin V assays.
- Bioinformatic analysis of differentially regulated proteins.
Main Results:
- Identified 10 differentially regulated proteins in TAL-resistant TNBC cells.
- Predicted alterations in EGF/FGF and AMPK signaling pathways.
- Predicted changes in phosphorylation/dephosphorylation dynamics in resistant cells.
Conclusions:
- The identified proteins may serve as therapeutic targets to overcome TAL resistance in TNBC.
- Elucidating these protein signatures provides insights into TAL resistance mechanisms.
- This research contributes to developing novel treatment strategies for advanced metastatic breast cancers.
