S1PR1 signaling in cancer: A current perspective

Anu, B; Namitha, N N; Harikumar, Kuzhuvelil B.

doi:10.1016/bs.apcsb.2020.12.006

Cited by 13 publications

(7 citation statements)

References 58 publications

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“…We also explored the upstream regulators of SAA1. S1P/S1PR1 signaling plays an important role in the growth, infiltration, metastasis, angiogenesis, and autophagy of various types of tumor cells by regulating the STAT, ERK, Akt and Rac pathways [ 21 ]. High expression of S1PR1 has been found to be involved in the proliferation and survival of ESCC cells by activating the STAT3 signaling pathway [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…Sphingosine 1-phosphate (S1P) is a bioactive lipid produced by the phosphorylation of sphingosine by sphingosine kinase (SPHK). Secreted extracellular S1P transmits signals by binding to five G-protein-coupled receptors (S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5) to regulate cell differentiation, proliferation, migration, and survival [ 21 ]. S1P/S1PR1 signaling plays an important role in the progression of various tumors [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via β-catenin activation

Li,

Tang,

Zhao

et al. 2024

Discov Onc

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Serum amyloid A1 (SAA1), an inflammation-related molecule, is associated with the malignant progression of many tumors. This study aimed to investigate the role of SAA1 in the progression of esophageal squamous cell carcinoma (ESCC) and its molecular mechanisms. The expression of SAA1 in ESCC tissues and cell lines was analyzed using bioinformatics analysis, western blotting, and reverse transcription-quantitative PCR (RT‒qPCR). SAA1-overexpressing or SAA1-knockdown ESCC cells were used to assess the effects of SAA1 on the proliferation, migration, apoptosis of cancer cells and the growth of xenograft tumors in nude mice. Western blotting, immunofluorescence and RT‒qPCR were used to investigate the relationship between SAA1 and β-catenin and SAA1 and sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 1 (S1PR1). SAA1 was highly expressed in ESCC tissues and cell lines. Overexpression of SAA1 significantly promoted the proliferation, migration and the growth of tumors in nude mice. Knockdown of SAA1 had the opposite effects and promoted the apoptosis of ESCC cells. Moreover, SAA1 overexpression promoted the phosphorylation of β-catenin at Ser675 and increased the expression levels of the β-catenin target genes MYC and MMP9. Knockdown of SAA1 had the opposite effects. S1P/S1PR1 upregulated SAA1 expression and β-catenin phosphorylation at Ser675 in ESCC cells. In conclusion, SAA1 promotes the progression of ESCC by increasing β-catenin phosphorylation at Ser675, and the S1P/S1PR1 pathway plays an important role in its upstream regulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via β-catenin activation

Li,

Tang,

Zhao

et al. 2024

Discov Onc

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“…In cancer development and progression, S1P “inside-out” signaling plays a critical role, and S1P acts on S1P receptors on the plasma membrane of the cancer cell itself and in the surrounding microenvironment via autocrine and paracrine modes of action [ 29 , 163 ]. The expression of S1PR1 and S1PR3 is often higher in breast cancer, suggesting that signaling through these receptors contributes to cancer growth and invasion [ 164 , 165 , 166 , 167 , 168 , 169 ]. S1P also acts on S1PR1 on vascular endothelial cells to induce angiogenesis [ 170 , 171 ] and on S1PR1 on immune cells to promote migration [ 172 ].…”

Section: S1p In Cancer Cells and The Interaction Between Cancer And T...mentioning

confidence: 99%

Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer

Nagahashi,

Miyoshi

2024

IJMS

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In recent years, newly emerging therapies, such as immune checkpoint inhibitors and antibody-drug conjugates, have further improved outcomes for breast cancer patients. However, recurrent and metastatic breast cancer often eventually develops resistance to these drugs, and cure is still rare. As such, the development of new therapies for refractory breast cancer that differ from conventional mechanisms of action is necessary. Sphingosine-1-phosphate (S1P) is a key molecule with a variety of bioactive activities, including involvement in cancer cell proliferation, invasion, and metastasis. S1P also contributes to the formation of the cancer microenvironment by inducing surrounding vascular- and lymph-angiogenesis and regulating the immune system. In this article, we outline the basic mechanism of action of S1P, summarize previous findings on the function of S1P in cancer cells and the cancer microenvironment, and discuss the clinical significance of S1P in breast cancer and the therapeutic potential of targeting S1P signaling.

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“…S1P can be exported out of cells where it activates autocrine or paracrine signaling through one or more of five different S1P receptors (S1PR1-5) [23,24]. S1PRs are G-protein coupled receptors that have partially convergent or antithetic effects [25][26][27]. For example, S1PR1 couples to Gi to evoke pro-migratory effects, while S1PR2 couples to Gi, Gq, and G12/13 to inhibit cell migration [28].…”

Section: Introductionmentioning

confidence: 99%

The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma

Perry,

Masand,

Vrzalikova

et al. 2024

Cancers

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Background: A total of 30–40% of diffuse large B cell lymphoma (DLBCL) patients will either not respond to the standard therapy or their disease will recur. The first-line treatment for DLBCL is rituximab and combination chemotherapy. This treatment involves the chemotherapy-induced recruitment of tumor-associated macrophages that recognize and kill rituximab-opsonized DLBCL cells. However, we lack insights into the factors responsible for the recruitment and functionality of macrophages in DLBCL tumors. Methods: We have studied the effects of the immunomodulatory lipid sphingosine-1-phosphate (S1P) on macrophage activity in DLBCL, both in vitro and in animal models. Results: We show that tumor-derived S1P mediates the chemoattraction of both monocytes and macrophages in vitro and in animal models, an effect that is dependent upon the S1P receptor S1PR1. However, S1P inhibited M1 macrophage-mediated phagocytosis of DLBCL tumor cells opsonized with the CD20 monoclonal antibodies rituximab and ofatumumab, an effect that could be reversed by an S1PR1 inhibitor. Conclusions: Our data show that S1P signaling can modulate macrophage recruitment and tumor cell killing by anti-CD20 monoclonal antibodies in DLBCL. The administration of S1PR1 inhibitors could enhance the phagocytosis of tumor cells and improve outcomes for patients.

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S1PR1 signaling in cancer: A current perspective

Cited by 13 publications

References 58 publications

SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via β-catenin activation

SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via β-catenin activation

Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer

The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma

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