S1PR1 Is Crucial for Accumulation of Regulatory T Cells in Tumors via STAT3

Priceman, Saul J.; Shen, Shudan; Wang, Lin; Deng, Jiehui; Yue, Chanyu; Kujawski, Maciej; Yu, Hua

doi:10.1016/j.celrep.2014.02.016

Cited by 79 publications

(64 citation statements)

References 30 publications

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“…It has also been reported that STAT3 regulated expression of S1PR1. Not only can STAT3 mediate S1PR1 expression, but S1PR1 activates STAT3 through the Jak2 tyrosine kinase [24,37,38]. We speculate that Gal-1 activates S1PR1 via activation of an "H-Ras -MEK/ERK -STAT3/S1PR1" axis in GC.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests a possible mechanism by which S1PR1 promotes invasion in GC cells through EMT. GC EMT is modulated by diverse intracellular cues, and can be triggered by various transcription factors, activation of numerous signaling pathways, such as the Ras-MAPK, PI3K/AKT, Wnt, Src, Hedgehog, or Rho pathways [45,46] S1PR1 may activate the "Jak/STAT3-Src" axis [38] [47], which can in turn induce GC EMT. However, the specific mechanism of action merits further exploration.…”

Section: Discussionmentioning

confidence: 99%

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Galectin-1 Promotes Metastasis in Gastric Cancer Through a Sphingosine-1-Phosphate Receptor 1-Dependent Mechanism

You

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increased expression of galectin-1 (Gal-1) in gastric cancer (GC) promotes metastasis and correlates with poor prognosis. The mechanisms by which Gal-1 promotes GC metastasis remain unknown. Methods: Gal-1and Sphingosine-1-phosphate receptor 1 (S1PR1) were determined by immunohistochemistry(IHC) and quantitative real time polymerase chain reaction (qRT-PCR) in GC specimens. Stably transfected Gal-1 or S1PR1 into SGC7901 and MGC-803 cells, western blot and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: Overexpression of Gal-1 enhanced expression of S1PR1 in SGC-7901 cells, and increased cell invasion, while knockdown Gal-1 in MGC-803 cells reduced S1PR1 expression and diminished invasion. Simultaneous knockdown of Gal-1 and overexpression of S1PR1 in MGC803 cells rescued invasive ability of MGC803 cells. S1PR1 was associated with expression of epithelial-to-mesenchymal transition (EMT) markers in vitro and in clinical samples. EMT induced in MGC-803 cells by TGF-β1 was accompanied by S1PR1 activation, while knockdown of S1PR1 reduced response to TGF-β1, suggest that Gal-1 promotes GC invasion by activating EMT through a S1PR1-dependent mechanism. Overexpression of S1PR1 promoted subcutaneous xenograft growth and pulmonary metastases, and enhanced expression of EMT markers. Conclusion: Galectin-1 promotes metastasis in gastric cancer through a S1PR1- dependent mechanism, our results indicate that targeting S1PR1 may be a novel strategy to treat GC metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Galectin-1 Promotes Metastasis in Gastric Cancer Through a Sphingosine-1-Phosphate Receptor 1-Dependent Mechanism

You

Wang

et al. 2018

Cell Physiol Biochem

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“…Extensive studies from our laboratory and others show that STAT3, a Signal Transducer and Activator of Transcription family protein critical for tumor cell survival and invasion, mediates the crosstalk between tumor cells and various immune cells, causing tumor immunosuppression (3,5-8). Our published results suggest that STAT3 activity within regulatory CD4 + T cells is critical for their tumor accumulation (3,9). By contrast, STAT3 intrinsic to CD8 + T cells inhibits their tumor infiltration (7).…”

Section: Introductionmentioning

confidence: 92%

“…We recently demonstrated that signaling of sphingosine-1-phosphate (S1P) and its receptor, S1PR1, which is critical for persistent STAT3 activation in tumor cells and tumor-associated immune cells (10), is essential for CD4 + T regulatory cell mobilization to tumor sites, thereby indirectly impacting accumulation of tumor-associated CD8 + T cells (9). However, little is understood about the detailed intrinsic molecular mechanisms by which CD8 + T cells home to tumor sites.…”

Section: Introductionmentioning

confidence: 99%

STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis

Yue

Shen

Deng

et al. 2015

Cancer Immunology Research

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One of the obstacles for cancer immunotherapy is the inefficiency of CD8+ T-cell recruitment to tumors. STAT3 has been shown to suppress CD8+ T-cell antitumor functions in various cancer models, in part by restricting accumulation of CD8+ T cells. However, the underlying molecular mechanism by which STAT3 in CD8+ T cells inhibits their accumulation in tumors remains to be defined. Here, we show that STAT3 signaling in CD8+ T cells inhibits chemokine CXCL10 production by tumor-associated myeloid cells via reducing IFNγ expression by T cells. We further demonstrate that ablating STAT3 in T cells allows expression of CXCR3, the receptor of CXCL10, on CD8+ T cells, resulting in efficient accumulation of CD8+ T cells at tumor sites. Blocking IFNγ or CXCR3 impairs the accumulation of STAT3-deficient CD8+ T cells in tumor and their antitumor effects. Together, our study reveals a negative regulation by STAT3 signaling in T cells on myeloid cell-T cell crosstalk through IFNγ/CXCR3/CXCL10, which is important for CD8+ T cells homing to tumors. Our results thus provide new insights applicable to cancer immunotherapy and adoptive T-cell strategies.

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“…It has previously been shown that S1PR1 is crucial for persistent STAT3 activation in cancer cells (16). Therefore, the present study examined STAT3 signaling pathways in the NPC cells following the overexpression or depletion of miR-133b.…”

Section: Mir-133b Regulates Stat3 Signaling In Npc Cellsmentioning

confidence: 90%

miR-133b, a microRNA targeting S1PR1, suppresses nasopharyngeal carcinoma cell proliferation

Cheng

Wang

2016

Experimental and Therapeutic Medicine

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Abstract. MicroRNAs (miRs) are a class of short and non-coding RNA molecules, which function as either oncogenes or tumor suppressors in the development of various human cancers, including nasopharyngeal carcinoma (NPC). The aim of the present study was to investigate the expression of miR-133b in NPC tissue samples, as compared with adjacent normal tissues, and to examine its roles and underlying mechanisms. Analysis using reverse transcription-quantitative polymerase chain reaction demonstrated that miR-133b was downregulated in NPC tissue samples, as compared with adjacent tissues. In vitro experiments using NPC cell lines transfected with miR-133b mimics or antisense oligonucleotides further demonstrated that the overexpression of miR-133b mimics impaired, whereas knockdown of its expression promoted, the proliferation of NPC cells. Sphingosine-1-phosphate receptor 1 (S1PR1) was predicted to be a target of miR-133b. Luciferase reporter assays showed that miR-133b inhibited the protein expression of S1PR1 by targeting its 3'-untranslated region. Furthermore, western blot analysis demonstrated that miR-133B altered the regulation of the signal transducer and activator of transcription-3 (STAT3) signaling pathway and the expression of downstream proteins in NPC cells. Therefore, the results of the present study suggested that a previously unknown miR-133b/S1PR1 molecular network may regulate NPC progression.

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S1PR1 Is Crucial for Accumulation of Regulatory T Cells in Tumors via STAT3

Cited by 79 publications

References 30 publications

Galectin-1 Promotes Metastasis in Gastric Cancer Through a Sphingosine-1-Phosphate Receptor 1-Dependent Mechanism

Galectin-1 Promotes Metastasis in Gastric Cancer Through a Sphingosine-1-Phosphate Receptor 1-Dependent Mechanism

STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis

miR-133b, a microRNA targeting S1PR1, suppresses nasopharyngeal carcinoma cell proliferation

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