Phosphoproteome Analysis Reveals Dynamic Heat Shock Protein 27 Phosphorylation in Tanshinone IIA-Induced Cell Death
Journal
Journal of Proteome Research
Journal Volume
19
Journal Issue
4
Pages
1620-1634
Date Issued
2020
Author(s)
Abstract
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. Copyright ? 2020 American Chemical Society.
SDGs
Other Subjects
complementary DNA; cysteine; ephrin receptor A2; heat shock protein 27; heat shock transcription factor 1; microtubule associated protein 2; mitogen activated protein kinase phosphatase 1; phosphopeptide; phosphoserine; phosphothreonine; phosphotyrosine; protein c jun; reactive oxygen metabolite; serine; tanshinone IIA; threonine; transcription factor; transcriptome; tyrosine; heat shock protein 27; tanshinone; Article; cell death; cell stress; controlled study; FLNC gene; flow cytometry; gene; human; human cell; image analysis; immunocytochemistry; ion exchange chromatography; liquid chromatography-mass spectrometry; phosphoproteomics; PLEC gene; priority journal; protein analysis; protein function; protein phosphorylation; real time polymerase chain reaction; Salvia miltiorrhiza; stomach cancer; transcriptomics; unfolded protein response; Western blotting; apoptosis; genetics; phosphorylation; tumor cell line; Abietanes; Apoptosis; Cell Line, Tumor; HSP27 Heat-Shock Proteins; Phosphorylation
Publisher
American Chemical Society
Type
journal article