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.

中文翻译：

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磷酸化蛋白质组分析揭示了丹参酮IIA诱导的细胞死亡中动态热休克蛋白27的磷酸化。

胃癌是全世界最常见的癌症之一。然而，尚未发现有效的治疗策略。多项研究表明，丹参酮IIA（TIIA）是从传统草药植物丹参（Salvia miltiorrhiza），对多种癌症都有潜在的活性。我们以前的研究表明TIIA可以诱导胃癌中的细胞死亡。但是，确切的信号通路反应仍不清楚。通过调节信号转导级联和许多细胞途径，翻译后修饰（PTM）在癌症的广泛生理过程中起着重要作用。在这里，我们整合了多层组学，即转录组学和动态磷酸化蛋白质组学，以阐明TIIA在胃癌中触发的调控网络。我们确定了响应TIIA的丝氨酸82处热休克蛋白27（HSP27）的磷酸化，这引起了活性氧（ROS）产生和未折叠的蛋白反应（UPR）。此外，细胞应力的积累增加了热激因子1（HSF1）的表达。另外，参与热激应激和凋亡的HSF1下游靶标也被TIIA处理的细胞激活。总之，这项研究执行了一种多组学方法，以阐明导致胃癌细胞死亡的全面TIIA响应网络。