Abstract
The spider peptide toxins HNTX-III and JZTX-I are a specific inhibitor and activator of TTX-S VGSCs, respectively. They play important roles in regulating MAT-LyLu cell metastasis in prostate cancer. In order to identify key biomarkers involved in the regulation of MAT-LyLu cell metastasis, iTRAQ-based quantitative phosphoproteomics analysis was performed on cells treated with HNTX-III, JZTX-I and blank. A total of 554 unique phosphorylated proteins and 1779 distinct phosphorylated proteins were identified, while 55 and 36 phosphorylated proteins were identified as differentially expressed proteins in HNTX-III and JZTX-I treated groups compared with control groups. Multiple bioinformatics analysis based on quantitative phosphoproteomics data suggested that the differentially expressed phosphorylated proteins and peptides were significantly associated with the migration and invasion of prostate tumors. Specifically, the toxins HNTX-III and JZTX-I have opposite effects on tumor formation and metastasis by regulating the expression and phosphorylation level of causal proteins. Herein, we highlighted three key proteins EEF2, U2AF2 and FLNC which were down-regulated in HNTX-III treated cells and up-regulated in JZTX-I treated cells. They played significant roles in cancer related physiological and pathological processes. The differentially expressed phosphorylated proteins identified in this study may serve as potential biomarkers for precision medicine for prostate cancer in the near future.
Highlights
To identify significant biomarkers involved in toxin regulation of prostate cancer, we conducted a quantitative phosphoproteomic analysis by iTRAQ integrated with LCMS/MS to identify differentially expressed phosphorylated proteins and phosphopeptides in high metastatic MAT-LyLu cells
The results indicated that the candidate proteins extension factor 2 (EEF2), U2AF2 and Filamin C (FLNC) could regulate the proliferation and metastasis of prostate cancer cells in a coordinated way with other differentially expressed phosphorylated proteins (DEPs) or their upstream and downstream key factors
Phosphoproteomics integrated with bioinformatics analysis showed that the above two toxins can regulate the proliferation and metastatic of cancer cells through mediating the expression level of significant biomarkers such as EEF2, U2AF2 and FLNC
Summary
Prostate cancer is one of the most common non-cutaneous genital malignancies in men, with an estimated 1.6 million cases and 366,000 deaths worldwide every year [1]. Metastatic disease is the leading cause of prostate-related death [2]. Metastatic prostate cancer resists hormone therapy and other conventional treatments [3,4]. High metastasis is one of the inevitable characteristics of most cancers, it is necessary and urgent to develop efficient targeted drugs to inhibit the high metastasis of prostate cancer. In the past few years, research on the role of ion channels in cancer have attached importance to the involvement of various channel types in cancer cell metabolism and the tumor microenvironment [5]
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