title: Osteopontin-a alters glucose homeostasis in anchorage-independent breast cancer cells.
abstract: Invasive breast tumor cells generate three splice variants of the metastasis gene osteopontin, while non-invasive breast cells express only the unspliced form or no osteopontin at all. One role for osteopontin in tumor progression is the support of anchorage-independence. Here we show that the full-length gene product, osteopontin-a, induces a gene expression profile that is associated with tissue remodeling and directed movement/sprouting. This occurs via signals through STAT1 and STAT3 to sn-glycero-3-phosphocholine. Osteopontin-a upregulates the levels of glucose in breast cancer cells, likely through STAT3 and its transcriptional targets apolipoprotein D and IGFBP5. The splice variants osteopontin-a and osteopontin-c may synergize, with each form activating signal transduction pathways that are distinct from the other. The elevated glucose is used by osteopontin-c dependent signals to generate chemical energy (Shi et al. submitted for publication). The splice variant-specific metabolic effects of osteopontin add a novel aspect to the pro-metastatic functions of this molecule.
authors.affiliation: University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Zhanquan
authors.initials: Z
authors.lastname: Shi
authors.affiliation: University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Mana
authors.initials: M
authors.lastname: Mirza
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kennedy
authors.affiliation: University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Weber
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D061986:MCF-7 Cells; D055432:Metabolomics; D009361:Neoplasm Invasiveness; D053495:Osteopontin / Q000378:metabolism*; D020033:Protein Isoforms; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D020033:Protein Isoforms; D053495:Osteopontin; D005947:Glucose
keywords: Cancer biology; Cytokine action; Glucose; Metabolic regulation; Metastasis