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Phosphoproteome Analysis Reveals Dynamic Heat Shock Protein 27 Phosphorylation in Tanshinone IIA-Induced Cell Death
journal contribution
posted on 2020-03-23, 17:09 authored by Chieh-Fan Yin, Shih-Chieh Kao, Chia-Lang Hsu, Yi-Wen Chang, Chantal Hoi Yin Cheung, Hsuan-Cheng Huang, Hsueh-Fen JuanGastric
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 omicstranscriptomics
and dynamic phosphoproteomicsto 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.