Circulating sphingosine-1-phosphate inversely correlates with chemotherapy-induced weight gain during early breast cancer

Pchejetski, Dimitri; Nunes, João; Sauer, Lysann; Sidhu, Jasmin; Sharma, Anand; Keun, Hector C.; Waxman, Jonathan; Stebbing, Justin

doi:10.1007/s10549-010-0968-y

Cited by 6 publications

(4 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have reported that aberrant S1P serum levels were found in animal models of cancer 14,30 . Moreover, serum levels of S1P were inversely correlated with chemotherapy-induced weight gain in women with breast cancer 47 . During the tumour development, high levels of S1P are produced through the upregulation of SPHK1 activity in cancer cells 14 .…”

Section: Article Nature Communications | Doi: 101038/ncomms5859mentioning

confidence: 95%

Hypothalamic S1P/S1PR1 axis controls energy homeostasis

et al. 2014

View full text Add to dashboard Cite

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.

show abstract

Section: Article Nature Communications | Doi: 101038/ncomms5859mentioning

confidence: 95%

Hypothalamic S1P/S1PR1 axis controls energy homeostasis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…S1P regulates the differentiation via MAPK pathways in a variety of cell types including osteoclasts, monocytes, placental trophoblasts, myoblasts and vascular smooth muscle cells (16,19,(22)(23)(24). In addition, a number of studies have shown that S1P and sphingosine kinases have multifunctional characteristics, including a correlation with weight gain in breast cancer patients, a sensitivity to acute myeloid leukemia cells, a chemotherapy sensor in prostate cancer and enhancing sensitivity to hormone-resistant prostate cancer (25)(26)(27)(28). ERK, p38 and JNK MAPKs are intracellular signaling pathways that play a pivotal role in numerous essential cell processes such as proliferation and differentiation (3,13,24).…”

Section: Introductionmentioning

confidence: 99%

Sphingosine-1-phosphate inhibits the adipogenic differentiation of 3T3-L1 preadipocytes

Moon

Jeong

Lee

et al. 2014

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits signals through G-protein-coupled receptors to control diverse biological processes. The novel biological activity of S1P in the adipogenesis of 3T3-L1 preadipocytes was identified in the present study. S1P significantly decreased lipid accumulation in maturing preadipocytes in a dose‑dependent manner. In order to understand the anti‑adipogenic effects of S1P, preadipocytes were treated with S1P, and the change in the expression of several adipogenic transcription factors and enzymes was investigated using quantitative RT-PCR. S1P downregulated the transcriptional levels of the peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding proteins and adiponectin, which are markers of adipogenic differentiation. The effects of S1P on the levels of mitogen‑activated protein kinase (MAPK) signals in preadipocytes were also investigated. The activation of JNK and p38 were downregulated by S1P treatment in human preadipocytes. In conclusion, the results of this study suggest that S1P alters fat mass by directly affecting adipogenesis. This is mediated by the downregulation of adipogenic transcription factors and by inactivation of the JNK and p38 MAPK pathways. Thus, selective targeting of the S1P receptors and sphingosine kinases may have clinical applications for the treatment of obesity.

show abstract

“…The only study to date investigating circulating S1P, to the authors' best knowledge, details the detrimental effect of circulating S1P with weight gain during chemotherapy among 21 patients [36]. In breast cancer cell lines, however, the use of tamoxifen and medroxyprogesterone result in the downregulation of S1PR3 and stimulation of S1PR2 with activation of autophagy of the breast cancer cells towards death, again demonstrating the detrimental role of S1P pathway activation in cancer [30].…”

Section: Discussionmentioning

confidence: 99%

Paradoxical Association of Postoperative Plasma Sphingosine-1-Phosphate with Breast Cancer Aggressiveness and Chemotherapy

Ramanathan

Ali

Sturgill

et al. 2017

Mediators of Inflammation

View full text Add to dashboard Cite

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that has been shown to serve an important regulatory function in breast cancer progression. This study analyzes plasma S1P levels in breast cancer patients undergoing adjuvant therapy as compared to healthy control volunteers. 452 plasma S1P samples among 158 breast cancer patients, along with 20 healthy control volunteers, were analyzed. Mean S1P levels did not significantly differ between cancer patients and controls. Smoking was associated with higher S1P levels in cancer patients. Baseline S1P levels had weak inverse correlation with levels of the inflammatory mediator interleukin- (IL-) 17 and CCL-2 and positive correlation with tumor necrosis factor alpha (TNF-α). Midpoint S1P levels during adjuvant therapy were lower than baseline, with near return to baseline after completion, indicating a relationship between chemotherapy and circulating S1P. While stage of disease did not correlate with plasma S1P levels, they were lower among patients with Her2-enriched and triple-negative breast cancer as compared to luminal-type breast cancer. Plasma S1P levels are paradoxically suppressed in aggressive breast cancer and during adjuvant chemotherapy, which raises the possibility that postoperative plasma S1P levels do not reflect S1P secretion from resected breast cancer.

show abstract

Circulating sphingosine-1-phosphate inversely correlates with chemotherapy-induced weight gain during early breast cancer

Cited by 6 publications

References 50 publications

Hypothalamic S1P/S1PR1 axis controls energy homeostasis

Hypothalamic S1P/S1PR1 axis controls energy homeostasis

Sphingosine-1-phosphate inhibits the adipogenic differentiation of 3T3-L1 preadipocytes

Paradoxical Association of Postoperative Plasma Sphingosine-1-Phosphate with Breast Cancer Aggressiveness and Chemotherapy

Contact Info

Product

Resources

About