Phosphoproteome Analysis Reveals Dynamic Heat Shock Protein 27 Phosphorylation in Tanshinone IIA-Induced Cell Death
| Autor: | Hsueh Fen Juan, Chia-Lang Hsu, Chieh Fan Yin, Yi Wen Chang, Hsuan Cheng Huang, Chantal Hoi Yin Cheung, Shih Chieh Kao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death 030102 biochemistry & molecular biology biology Chemistry HSP27 Heat-Shock Proteins Cancer Apoptosis General Chemistry medicine.disease Biochemistry Salvia miltiorrhiza Cell biology 03 medical and health sciences 030104 developmental biology Hsp27 Heat shock protein Cell Line Tumor Abietanes Unfolded protein response medicine biology.protein Signal transduction Phosphorylation HSF1 |
| Zdroj: | Journal of proteome research. 19(4) |
| ISSN: | 1535-3907 |
| Popis: | Gastric cancer is one of the most common types of cancer worldwide. Nevertheless, effective therapeutic strategies have not yet been discovered. Several studies have shown that tanshinone IIA (TIIA), which is extracted from the traditional herbal medicine plant Danshen (Salvia miltiorrhiza), has potential activity against many kinds of cancer. Our previous research demonstrated that TIIA can induce cell death in gastric cancer. However, the exact signaling pathway response is still unclear. Post-translational modification (PTM) plays a significant role in a wide range of physiological processes in cancer, via regulation of both signal transduction cascades and many cellular pathways. Here, we integrated multilayer omics-transcriptomics and dynamic phosphoproteomics-to elucidate the regulatory networks triggered by TIIA in gastric cancer. We identified the phosphorylation of heat shock protein 27 (HSP27) at serine 82 in response to TIIA, which caused reactive oxygen species (ROS) production and unfolded protein response (UPR). Moreover, the accumulation of cellular stress increased the expression of heat shock factor 1 (HSF1). In addition, the downstream targets of HSF1, which were involved in heat shock stress and apoptosis, were also activated in TIIA-treated cells. In conclusion, this study performs a multiomic approach to clarify a comprehensive TIIA-responsive network leading to cell death in gastric cancer. |
| Databáze: | OpenAIRE |
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