Sphingosine kinase 1 Isoform-Specific interactions in breast cancer

Yagoub, D; Wilkins, MR; Lay, AJ; Kaczorowski, DC; Hatoum, D; Bajan, S; Hutvagner, G; Lai, JH; Wu, W; Martiniello-Wilks, R; Xia, P; McGowan, EM

Sphingosine kinase 1 Isoform-Specific interactions in breast cancer

Yagoub, D Wilkins, MR Lay, AJ Kaczorowski, DC Hatoum, D Bajan, S

Hutvagner, G

Lai, JH Wu, W Martiniello-Wilks, R

Xia, P McGowan, EM

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Publication Type:: Journal Article
Citation:: Molecular Endocrinology, 2014, 28 (11), pp. 1899 - 1915
Issue Date:: 2014-01-01

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Field	Value	Language
dc.contributor.author	Yagoub, D	en_US
dc.contributor.author	Wilkins, MR	en_US
dc.contributor.author	Lay, AJ	en_US
dc.contributor.author	Kaczorowski, DC	en_US
dc.contributor.author	Hatoum, D	en_US
dc.contributor.author	Bajan, S https://orcid.org/0000-0001-6934-5240	en_US
dc.contributor.author	Hutvagner, G https://orcid.org/0000-0002-7231-9446	en_US
dc.contributor.author	Lai, JH	en_US
dc.contributor.author	Wu, W	en_US
dc.contributor.author	Martiniello-Wilks, R https://orcid.org/0000-0002-0038-3430	en_US
dc.contributor.author	Xia, P	en_US
dc.contributor.author	McGowan, EM https://orcid.org/0000-0001-6371-3751	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	Molecular Endocrinology, 2014, 28 (11), pp. 1899 - 1915	en_US
dc.identifier.issn	0888-8809	en_US
dc.identifier.uri	http://hdl.handle.net/10453/35265
dc.description.abstract	© 2014 by the Endocrine Society. 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, SK143kDa and SK151kDa, have been identified; however, the 51kDa variant is predominant in breast cancer cells. No studies have investigated the protein-protein interactions of the 51kDa 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 immunopre-cipitates, 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 assupervillin, 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 43kDa 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 51kDa isoform of SK1. In this report, we have identified common and isoform-specificSK1-interacting partners that provide insight into the molecular mechanisms that drive SK1-mediated oncogenicity.	en_US
dc.relation.ispartof	Molecular Endocrinology	en_US
dc.relation.isbasedon	10.1210/me.2013-1423	en_US
dc.subject.classification	Endocrinology & Metabolism	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Breast Neoplasms	en_US
dc.subject.mesh	Sphingosine	en_US
dc.subject.mesh	Phosphotransferases (Alcohol Group Acceptor)	en_US
dc.subject.mesh	Lysophospholipids	en_US
dc.subject.mesh	DNA-Binding Proteins	en_US
dc.subject.mesh	Protein Isoforms	en_US
dc.subject.mesh	Cell Adhesion	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Latent TGF-beta Binding Proteins	en_US
dc.subject.mesh	Dipeptidyl-Peptidases and Tripeptidyl-Peptidases	en_US
dc.subject.mesh	MCF-7 Cells	en_US
dc.subject.mesh	Calcium-Binding Proteins	en_US
dc.subject.mesh	Microfilament Proteins	en_US
dc.title	Sphingosine kinase 1 Isoform-Specific interactions in breast cancer	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	28	en_US
utslib.for	0604 Genetics	en_US
utslib.for	1107 Immunology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	07 Agricultural and Veterinary Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	closed_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	28	en_US

Abstract:

© 2014 by the Endocrine Society. 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, SK143kDa and SK151kDa, have been identified; however, the 51kDa variant is predominant in breast cancer cells. No studies have investigated the protein-protein interactions of the 51kDa 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 immunopre-cipitates, 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 assupervillin, 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 43kDa 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 51kDa isoform of SK1. In this report, we have identified common and isoform-specificSK1-interacting partners that provide insight into the molecular mechanisms that drive SK1-mediated oncogenicity.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/35265