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S1P Cancer

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https://www.readbyqxmd.com/read/29351902/targeting-the-sphk1-s1p-s1pr1-axis-that-links-obesity-chronic-inflammation-and-breast-cancer-metastasis
#1
Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P Terracina, Nitai C Hait, Jeremy C Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) which mediates cancer pathogenesis. A high fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29234668/a-genome-wide-screen-for-fty720-sensitive-mutants-reveals-genes-required-for-ros-homeostasis
#2
Kanako Hagihara, Kanako Kinoshita, Kouki Ishida, Shihomi Hojo, Yoshinori Kameoka, Ryosuke Satoh, Teruaki Takasaki, Reiko Sugiura
Fingolimod hydrochloride (FTY720), a sphingosine-1-phosphate (S1P) analogue, is an approved immune modulator for the treatment of multiple sclerosis (MS). Notably, in addition to its well-known mode of action as an S1P modulator, accumulating evidence suggests that FTY720 induces apoptosis in various cancer cells via reactive oxygen species (ROS) generation. Although the involvement of multiple signaling molecules, such as JNK (Jun N-terminal kinase), Akt (alpha serine/threonine-protein kinase) and Sphk has been reported, the exact mechanisms how FTY720 induces cell growth inhibition and the functional relationship between FTY720 and these signaling pathways remain elusive...
November 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29229990/tumor-suppressor-p53-links-ceramide-metabolism-to-dna-damage-response-through-alkaline-ceramidase-2
#3
Ruijuan Xu, Monica Garcia-Barros, Sally Wen, Fang Li, Chih-Li Lin, Yusuf A Hannun, Lina M Obeid, Cungui Mao
p53 mediates the DNA damage response (DDR) by regulating the expression of genes implicated in cell cycle arrest, senescence, programmed cell death (PCD), and metabolism. Herein we demonstrate that human alkaline ceramidase 2 (ACER2) is a novel transcriptional target of p53 and that its transactivation by p53 mediates the DDR. We found that p53 overexpression or its activation by ionizing radiation (IR) upregulated ACER2 in cells. Two putative p53 responsive elements (p53REs) were found in its first intron of the ACER2 gene, and Chromatin Immunoprecipitation (ChIP) assays in combination with promoter activity assays demonstrated that these p53REs are the bona fide p53 binding sites that mediate ACER2 transactivation by p53...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29223361/evidence-suggests-sphingosine-1-phosphate-might-be-actively-generated-degraded-and-transported-to-extracellular-spaces-with-increased-s1p2-and-s1p3-expression-in-colon%C3%A2-cancer
#4
Baasanjav Uranbileg, Takeshi Nishikawa, Hitoshi Ikeda, Makoto Kurano, Masaya Sato, Daisuke Saigusa, Junken Aoki, Toshiaki Watanabe, Yutaka Yatomi
BACKGROUND: A pivotal role of sphingosine 1-phosphate (S1P) in cancer has been suggested based on the ceramide-S1P rheostat theory that the intracellular balance between prosurvival S1P and proapoptotic ceramide determines cell fate. Upregulation of S1P-generating sphingosine kinases (SKs) and downregulation of S1P-degrading S1P lyase (SPL) might increase intracellular S1P levels to exert a prosurvival effect in cancer in general, such as colon cancer. However, we recently observed a distinct S1P metabolism in hepatocellular carcinoma tissues that increased SPL mRNA levels with reduced S1P levels...
November 21, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29186783/altered-leukocyte-sphingolipid-pathway-in-breast-cancer
#5
(no author information available yet)
Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC) patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P) receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients...
November 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29149079/sphingosine-1-phosphate-s1p-signaling-in-glioblastoma-multiforme-a-systematic-review
#6
REVIEW
Shailaja Mahajan-Thakur, Sandra Bien-Möller, Sascha Marx, Henry Schroeder, Bernhard H Rauch
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29147072/paradoxical-association-of-postoperative-plasma-sphingosine-1-phosphate-with-breast-cancer-aggressiveness-and-chemotherapy
#7
Rajesh Ramanathan, Ali Raza, Jamie Sturgill, Debra Lyon, Jessica Young, Nitai C Hait, Kazuaki Takabe
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...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29147025/sphingolipid-metabolism-in-cancer-signalling-and-therapy
#8
REVIEW
Besim Ogretmen
Sphingolipids, including the two central bioactive lipids ceramide and sphingosine-1-phosphate (S1P), have opposing roles in regulating cancer cell death and survival, respectively, and there have been exciting developments in understanding how sphingolipid metabolism and signalling regulate these processes in response to anticancer therapy. Recent studies have provided mechanistic details of the roles of sphingolipids and their downstream targets in the regulation of tumour growth and response to chemotherapy, radiotherapy and/or immunotherapy using innovative molecular, genetic and pharmacological tools to target sphingolipid signalling nodes in cancer cells...
November 17, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29136008/automated-tracking-and-quantification-of-angiogenic-vessel-formation-in-3d-microfluidic-devices
#9
Mengmeng Wang, Lee-Ling Sharon Ong, Justin Dauwels, H Harry Asada
Angiogenesis, the growth of new blood vessels from pre-existing vessels, is a critical step in cancer invasion. Better understanding of the angiogenic mechanisms is required to develop effective antiangiogenic therapies for cancer treatment. We culture angiogenic vessels in 3D microfluidic devices under different Sphingosin-1-phosphate (S1P) conditions and develop an automated vessel formation tracking system (AVFTS) to track the angiogenic vessel formation and extract quantitative vessel information from the experimental time-lapse phase contrast images...
2017: PloS One
https://www.readbyqxmd.com/read/29078883/doxorubicin-effect-is-enhanced-by-sphingosine-1-phosphate-signaling-antagonist-in-breast-cancer
#10
Eriko Katsuta, Li Yan, Masayuki Nagahashi, Ali Raza, Jamie L Sturgill, Debra E Lyon, Omar M Rashid, Nitai C Hait, Kazuaki Takabe
BACKGROUND: Doxorubicin is one of the most commonly used chemotherapeutic drugs for breast cancer; however, its use is limited by drug resistance and side effects. We hypothesized that adding FTY720, a sphingosine-1-phosphate (S1P) receptor functional antagonist, to doxorubicin would potentiate its effects by suppression of drug-induced inflammation. MATERIALS AND METHODS: The Cancer Genome Atlas, Gene Expression Omnibus data sets, and National Cancer Institute-60 panel were used for gene expressions and gene set enrichment analysis...
November 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29057430/regulation-and-function-of-sphingosine-kinase-2-in-diseases
#11
Dan-Dan Song, Jun-Hao Zhou, Rui Sheng
Sphingosine kinase functions to phosphorylate sphingosine to sphingosine 1-phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Although SphK1 and SphK2 share high sequence similarity, SphK2 has distinct distribution, regulation and function. SphK2 is involved in the pathological processes of varieties of diseases including cancer, neurodegenerative disorders, stroke, cardiovascular diseases and inflammation...
October 19, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/29055687/sphingosine-kinase-1-in-breast-cancer
#12
REVIEW
Kurt Geffken, Sarah Spiegel
Breast cancer affects 1 out of 8 women in the US and is the second highest cause of death from cancer for women, leading to considerable research examining the causes, progression, and treatment of breast cancer. Over the last two decades, sphingosine-1-phosphate (S1P), a potent sphingolipid metabolite, has been implicated in many processes important for breast cancer including growth, progression, transformation and metastasis, and is the focus of this review. In particular, one of the kinases that produces S1P, sphingosine kinase 1 (SphK1), has come under increasing scrutiny as it is commonly upregulated in breast cancer cells and has been linked with poorer prognosis and progression, possibly leading to resistance to certain anti-cancer therapies...
October 16, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29036438/a-selective-sphingosine-1-phosphate-receptor-1-agonist-sew-2871-aggravates-gastric-cancer-by-recruiting-myeloid-derived-suppressor-cells
#13
Yujing Zhou, Feng Guo
The immune status of tumor microenvironment in gastric cancer is poorly understood, which limits the development of novel strategies in this field. Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)-mediated effect of S1P in gastric cancer. We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signaling. Tumor-infiltrating lymphocytes (TILs) were isolated and analyzed using flow cytometry...
October 3, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29028945/sphingosine-kinase-1-expression-in-peritoneal-macrophages-is-required-for-colon-carcinogenesis
#14
Hideki Furuya, Paulette M Tamashiro, Yoshiko Shimizu, Kayoko Iino, Rafael Peres, Runpu Chen, Yijun Sun, Yusuf A Hannun, Lina M Obeid, Toshihiko Kawamori
Accumulating evidence suggests that the sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P) pathway plays a pivotal role in colon carcinogenesis. Our previous studies indicate that the SphK1/S1P pathway mediates colon carcinogenesis at least by regulating COX-2 expression and prostaglandin E2 (PGE2) production. However, the mechanisms by which this pathway regulates colon carcinogenesis are still unclear. First, we show that SphK1 deficient mice significantly attenuated azoxymethane (AOM)-induced colon carcinogenesis as measured by colon tumor incidence, multiplicity, and volume...
September 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28991193/sphingosine-kinase-1-and-sphingosine-1-phosphate-signaling-in-colorectal-cancer
#15
REVIEW
Yonghua Bao, Yongchen Guo, Chenglan Zhang, Fenghua Fan, Wancai Yang
Sphingosine kinase 1 (Sphk1) is a highly conserved lipid kinase that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P). Growing studies have demonstrated that Sphk1 is overexpressed in various types of solid cancers and can be induced by growth factors, cytokines, and carcinogens, leading to the increase of S1P production. Subsequently, the increased Sphk1/S1P facilitates cancer cell proliferation, mobility, angiogenesis, invasion, and metastasis. Therefore, Sphk1/S1P signaling plays oncogenic roles...
October 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28968647/genetic-deletion-of-sphingosine-kinase-1-suppresses-mouse-breast-tumor-development-in-a-her2-transgenic-model
#16
Yoshiko Shimizu, Hideki Furuya, Paulette M Tamashiro, Kayoko Iino, Owen T M Chan, Steve Goodison, Ian Pagano, Kanani Hokutan, Rafael Peres, Lenora W M Loo, Brenda Hernandez, Aung Naing, Clayton D K Chong, Charles J Rosser, Toshihiko Kawamori
Aberrant sphingolipid metabolism has been reported to promote breast cancer progression. Sphingosine kinase 1 (SphK1) is a key metabolic enzyme for the formation of pro-survival S1P from pro-apoptotic ceramide. The role of SphK1 in breast cancer has been well studied in estrogen receptor (ER)-positive breast cancer, however, its role in human epidermal growth factor 2 (HER2)-positive breast cancer remains unclear. Here we show that genetic deletion of SphK1 significantly reduced mammary tumor development with reduced tumor incidence and multiplicity in the MMTV-neu transgenic mouse model...
September 11, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28942351/sphingosine-1-phosphate-and-cancer
#17
REVIEW
Nigel J Pyne, Ashref El Buri, David R Adams, Susan Pyne
The bioactive lipid, sphingosine 1-phosphate (S1P) is produced by phosphorylation of sphingosine and this is catalysed by two sphingosine kinase isoforms (SK1 and SK2). Here we discuss structural functional aspects of SK1 (which is a dimeric quaternary enzyme) that relate to coordinated coupling of membrane association with phosphorylation of Ser225 in the 'so-called' R-loop, catalytic activity and protein-protein interactions (e.g. TRAF2, PP2A and Gq). S1P formed by SK1 at the plasma-membrane is released from cells via S1P transporters to act on S1P receptors to promote tumorigenesis...
September 15, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28938552/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#18
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912626/clinical-impact-of-sphingosine-1-phosphate-in-breast-cancer
#19
REVIEW
Junko Tsuchida, Masayuki Nagahashi, Kazuaki Takabe, Toshifumi Wakai
Breast cancer metastasizes to lymph nodes or other organs, which determine the prognosis of patients. It is difficult to cure the breast cancer patients with distant metastasis due to resistance to drug therapies. Elucidating the underlying mechanisms of breast cancer metastasis and drug resistance is expected to provide new therapeutic targets. Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive lipid mediator that regulates many cellular functions, including proliferation, migration, survival, angiogenesis/lymphangiogenesis, and immune responses...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28869494/-dicing-and-splicing-sphingosine-kinase-and-relevance-to-cancer
#20
REVIEW
Nahal Haddadi, Yiguang Lin, Ann M Simpson, Najah T Nassif, Eileen M McGowan
Sphingosine kinase (SphK) is a lipid enzyme that maintains cellular lipid homeostasis. Two SphK isozymes, SphK1 and SphK2, are expressed from different chromosomes and several variant isoforms are expressed from each of the isozymes, allowing for the multi-faceted biological diversity of SphK activity. Historically, SphK1 is mainly associated with oncogenicity, however in reality, both SphK1 and SphK2 isozymes possess oncogenic properties and are recognized therapeutic targets. The absence of mutations of SphK in various cancer types has led to the theory that cancer cells develop a dependency on SphK signaling (hyper-SphK signaling) or "non-oncogenic addiction"...
September 2, 2017: International Journal of Molecular Sciences
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