O-56 High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1 and ERK-1/2 is associated with development of tamoxifen resistance in ER positive breast cancer patients

Watson, Carol; Long, Jaclyn; Orange, Clare; Tannahill, Carol; Mallon, Elizabeth; McGlynn, Liane; Pyne, Susan; Pyne, Nigel J.; Edwards, Joanne

doi:10.1016/j.ejcsup.2010.06.057

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A member of the large PP2C family of protein phosphatases, the oncogenic PPM1G protein is a negative regulator of the p53 tumor suppressor response pathway (79). Whether it has any phosphatase activity on SK1 will be interesting to determine, particularly in the context of recent studies linking ERK-mediated phosphorylation of SK1 with breast cancer progression through increased cell growth and migration (80).…”

mentioning

confidence: 99%

Sphingosine Kinase 1 Isoform-Specific Interactions in Breast Cancer

Yagoub

Wilkins

Lay

et al. 2014

Molecular Endocrinology

View full text Add to dashboard Cite

Sphingosine kinase 1 (SK1) is a signaling enzyme that catalyzes the formation of sphingosine-1-phosphate. Overexpression of SK1 is causally associated with breast cancer progression and resistance to therapy. SK1 inhibitors are currently being investigated as promising breast cancer therapies. Two major transcriptional isoforms, SK143 kDa and SK151 kDa, have been identified; however, the 51 kDa variant is predominant in breast cancer cells. No studies have investigated the protein-protein interactions of the 51 kDa isoform and whether the two SK1 isoforms differ significantly in their interactions. Seeking an understanding of the regulation and role of SK1, we used a triple-labeling stable isotope labeling by amino acids in cell culture-based approach to identify SK1-interacting proteins common and unique to both isoforms. Of approximately 850 quantified proteins in SK1 immunoprecipitates, a high-confidence list of 30 protein interactions with each SK1 isoform was generated via a meta-analysis of multiple experimental replicates. Many of the novel identified SK1 interaction partners such as supervillin, drebrin, and the myristoylated alanine-rich C-kinase substrate-related protein supported and highlighted previously implicated roles of SK1 in breast cancer cell migration, adhesion, and cytoskeletal remodeling. Of these interactions, several were found to be exclusive to the 43 kDa isoform of SK1, including the protein phosphatase 2A, a previously identified SK1-interacting protein. Other proteins such as allograft inflammatory factor 1-like protein, the latent-transforming growth factor β-binding protein, and dipeptidyl peptidase 2 were found to associate exclusively with the 51 kDa isoform of SK1. In this report, we have identified common and isoform-specific SK1-interacting partners that provide insight into the molecular mechanisms that drive SK1-mediated oncogenicity.

show abstract

mentioning

confidence: 99%

Sphingosine Kinase 1 Isoform-Specific Interactions in Breast Cancer

Yagoub

Wilkins

Lay

et al. 2014

Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…These receptors are exclusively coupled to heterotrimeric G proteins and Rho or Rac to control various effector systems, including adenylate cyclase, phospholipases C and D and extracellular-regulated p38 mitogen-activated protein, c-Jun N-terminal and non-receptor tyrosine kinase ( 17 – 19 ). S1PR1 and S1PR3 mediate potent stimulation of migration and invasion of tumour cells by inducing ERK activation, whereas S1PR2 exhibits an inhibitory effect via Rho activation and Rac inhibition ( 20 – 23 ). Therefore, the role of S1PRs in cancer remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Expression of sphingosine‑1‑phosphate receptor 2 is correlated with migration and invasion of human colon cancer cells: A preliminary clinical study

Yan

Chen

et al. 2022

Oncol Lett

View full text Add to dashboard Cite

Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that serves as a potent mediator of cell proliferation, differentiation and apoptosis by binding to S1P receptors (S1PRs). S1P signalling is involved in the pathogenesis of numerous types of disease, including cancer. To the best of our knowledge, however, little is known about the expression patterns of S1PRs and their role in human colorectal cancer (CRC) cell migration and invasion. The aim of the present study was to investigate the role of S1P signalling in the metastasis of colon cancer cells and the expression of S1PRs in patients with CRC. The protein and mRNA expression levels of S1PRs and sphingosine kinases (SPHKs) in 55 patients with CRC were detected by western blotting (WB), immunohistochemical (IHC) analysis and reverse transcription-quantitative PCR. The levels of S1P in serum from patients and healthy individuals were quantified by ELISA. S1PRs antagonists JTE013, FTY720 and S1PR2-small interfering (si)RNA were used to determine the role of S1PR2 in human CRC LOVO and SW480 cell lines. Migration and invasion assays were performed for functional analysis. The levels of S1P in serum were significantly increased in patients with CRC compared with healthy individuals. The relative mRNA expression levels of S1PR2 were significantly downregulated in tumour compared with normal tissue, whereas S1PR1 and SPHK1 were upregulated. WB showed that 58% (32/55 cases) of patients presented downregulated S1PR2 protein expression. IHC analysis indicated that expression of S1PR2 was lower in tumour than in normal tissue in 65.5% (36/55 cases) of patients. Exogenous addition of S1P promoted migration and invasion in the different cell types. S1P stimulated the migration and invasion of SW480 cells. The inhibition of S1PR2 by JTE013 or S1PR2-siRNA significantly promoted the migration and invasion of SW480 cells, while FTY720 reversed these effects. The present study indicated that expression levels of S1PRs, particularly S1PR2, were associated with migration and invasion of CRC cells. The present findings revealed a novel mechanism by which S1P inhibited tumour cell migration and invasion via a S1PR2-dependent pathway, suggesting that S1PR2 may be a therapeutic target for treatment of colon cancer.

show abstract

O-56 High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1 and ERK-1/2 is associated with development of tamoxifen resistance in ER positive breast cancer patients

Cited by 2 publications

References 0 publications

Sphingosine Kinase 1 Isoform-Specific Interactions in Breast Cancer

Sphingosine Kinase 1 Isoform-Specific Interactions in Breast Cancer

Expression of sphingosine‑1‑phosphate receptor 2 is correlated with migration and invasion of human colon cancer cells: A preliminary clinical study

Contact Info

Product

Resources

About