Osteopontin-a alters glucose homeostasis in anchorage-independent breast cancer cells

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• 作者：Zhanquan Shi ; Mana Mirza ; Bo Wang ; Michael A. Kennedy ; Georg F. Weber
• 关键词：Cancer biology ; Metabolic regulation ; Glucose ; Cytokine action ; Metastasis
• 刊名：Cancer Letters
• 出版年：1 March, 2014
• 年：2014
• 卷：344
• 期：1
• 页码：47-53
• 全文大小：1323 K

文摘

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.