S1PR1 promotes proliferation and inhibits apoptosis of esophageal squamous cell carcinoma through activating STAT3 pathway

Abstract

Background Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, which lacks effective biomarkers for prognosis. Therefore, it is urgent to explore new potential molecular markers to discriminate patients with poorer survival in ESCC. Methods Bioinformatics analysis, qRT-PCR, and western blot were applied to investigate S1PR1 expression. CCK-8 assay, colony formation assay, flow cytometry dual staining assay, and immunofluorescence were performed to examine cell proliferation ability and apoptosis rate. Mouse xenograft model of TE-13 cells was established to confirm the roles of S1PR1 in vivo. Gene set enrichment analysis (GSEA) was used to investigate the downstream signaling pathways related to S1PR1 functions. Co-IP was performed to verify the direct binding of S1PR1 and STAT3. Western blot was applied to determine the phosphorylation level of STAT3. Immunohistochemistry was conducted to identify protein expression of S1PR1 and p- STAT3 in tumor tissues. Results In the present study, we found that S1PR1 expression was higher in ESCC patients and was a potential biomarker for poor prognosis. Silencing S1PR1 expression inhibited proliferation, and increased apoptosis of ESCC cells, while overexpression of S1PR1 had opposite effects. Mechanistically, S1PR1 played the roles of promoting proliferation and attenuating apoptosis through directly activating p-STAT3. Furthermore, in vivo experiments verified this mechanism. Conclusion Our findings indicated that S1PR1 enhanced proliferation and inhibited apoptosis of ESCC cells by activating STAT3 signaling pathway. S1PR1 may serve as a prognostic biomarker for clinical applications. Electronic supplementary material The online version of this article (10.1186/s13046-019-1369-7) contains supplementary material, which is available to authorized users.

RETRACTED: Coinhibition of S1PR1 and GP130 by siRNA‐loaded alginate‐conjugated trimethyl chitosan nanoparticles robustly blocks development of cancer cells

“…The outcomes of our study confirmed that cancer cell treatment with siRNA-loaded NPs significantly decreased colony formation ability of tumor cells, which was correlated with the apoptosis induction in these cells. Consistently, it has been shown that S1PR1 inhibited apoptosis and promoted the proliferation of squamous cancer cells through activating the STAT3 pathway (Y. Liu et al, 2019). In another study, it was shown that S1P through signaling involving S1PR1 stimulates proliferation and its targeting leads to apoptosis induction (Wang, Huang, & Ding, 2018).…”

Development of an Immune-Related Risk Signature for Predicting Prognosis in Lung Squamous Cell Carcinoma

“…S1PR1, EDNRB and FGFR4 were predominantly signatures that represented the modules. They are tightly correlated with cancer development and progression (Tanaka et al, 2014;Lang and Teng, 2019;Liu Y. et al, 2019), and involved in the egress of T cells from lung tissue in tumor infiltrating lymphocytes conditions (Mackay et al, 2015). Seven TFs were found to be key regulators of these OS-related IRGs.…”

A Methylation-based nomogram for predicting survival in patients with lung adenocarcinoma

“…Recent studies demonstrated that the expression patterns of S1PR1 are altered in several tumors. Many researchers found that a positive regulatory interaction with signal transducer and activator of transcription 3 (STAT3) is involved in cancer tumorigenesis, metastasis and chemoresistance, such as gastric cancer [37], esophageal squamous cell carcinoma [38] and colorectal cancer [39]. In our study, we found that the expression of S1PR1 was signi cantly lower in LUAD patients, regulated by hypermethylation at cg07400091.…”