Osteopontin-a alters glucose homeostasis in anchorage-independent breast cancer cells.
Osteopontin-a alters glucose homeostasis in anchorage-independent breast cancer cells.
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DOI:
10.1016/j.canlet.2013.10.008
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发表时间:
2014-03-01
期刊:
影响因子:
9.7
通讯作者:
Weber, Georg F.
中科院分区:
文献类型:
--
作者:
Shi, Zhanquan;Mirza, Mana;Wang, Bo;Kennedy, Michael A.;Weber, Georg F.
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 snglycero-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. manuscript submitted). The splice variant-specific metabolic effects of osteopontin add a novel aspect to the pro-metastatic functions of this molecule.
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