SIBLING Expression Patterns in Duct Epithelia Reflect the Degree of Metabolic Activity

Ogbureke, Kalu U.E.; Fisher, Larry W.

doi:10.1369/jhc.6a7075.2007

Cited by 79 publications

(74 citation statements)

References 44 publications

(56 reference statements)

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“…22 Figure 1A shows that the mitochondrial mass is specifically increased in MCF7 cells in coculture maintained in high glutamine media, as compared with no glutamine media. Importantly, the mitochondrial mass is augmented specifically in the epithelial cancer cells, but not in the fibroblast compartment.…”

Section: Resultsmentioning

confidence: 99%

Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells

Zhao

Flomenberg

et al. 2011

Cancer Biology & Therapy

146

122

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Glutamine metabolism is crucial for cancer cell growth via the generation of intermediate molecules in the tricarboxylic acid (TCA) cycle, antioxidants and ammonia. The goal of the current study was to evaluate the effects of glutamine on metabolism in the breast cancer tumor microenvironment, with a focus on autophagy and cell death in both epithelial and stromal compartments. For this purpose, MCF7 breast cancer cells were cultured alone or co-cultured with nontransformed fibroblasts in media containing high glutamine and low glucose (glutamine +) or under control conditions, with no glutamine and high glucose (glutamine -). Here, we show that MCF7 cells maintained in co-culture with glutamine display increased mitochondrial mass, as compared with control conditions. Importantly, treatment with the autophagy inhibitor chloroquine abolishes the glutamine-induced augmentation of mitochondrial mass. It is known that loss of caveolin-1 (Cav-1) expression in fibroblasts is associated with increased autophagy and an aggressive tumor microenvironment. Here, we show that Cav-1 downregulation which occurs in fibroblasts maintained in co-culture specifically requires glutamine. Interestingly, glutamine increases the expression of autophagy markers in fibroblasts, but decreases expression of autophagy markers in MCF7 cells, indicating that glutamine regulates the autophagy program in a compartment-specific manner. Functionally, glutamine protects MCF7 cells against apoptosis, via the upregulation of the anti-apoptotic and anti-autophagic protein TIGAR. Also, we show that glutamine cooperates with stromal fibroblasts to confer tamoxifen-resistance in MCF7 cancer cells. Finally, we provide evidence that co-culture with fibroblasts (1) promotes glutamine catabolism, and (2) decreases glutamine synthesis in MCF7 cancer cells. Taken together, our findings suggest that autophagic fibroblasts may serve as a key source of energy-rich glutamine to fuel cancer cell mitochondrial activity, driving a vicious cycle of catabolism in the tumor stroma and anabolic tumor cell expansion.

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Section: Resultsmentioning

confidence: 99%

Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells

Zhao

Flomenberg

et al. 2011

Cancer Biology & Therapy

146

122

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“…Matrix extracellular phosphoglycoprotein (MEPE) was originally discovered in tumours causing osteomalacia and was shown at that time to be expressed (mRNA only) predominantly in bone and brain with "very low levels of expression" in lung, kidney and placenta 122 . Recent studies have demonstrated that all five members of the SIBLING family are expressed in metabolically active ductal epithelial cells of the salivary gland and kidney 14,15 and all but MEPE were expressed in eccrine sweat ducts 16 . MEPE expression appears to be limited to ductal cells that actively transport phosphate 16 .…”

Section: Box 1 Expression and Distribution Of Siblings In Normal Tissuesmentioning

confidence: 99%

Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer

et al. 2008

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Numerous components and pathways are involved in the complex interplay between cancer cells and their environment. The family of glycophosphoproteins comprising osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein -small integrin-binding ligand N-linked glycoproteins (SIBLINGs) -are emerging as important players in many stages of cancer progression. From their detection in various human cancers to the demonstration of their key functional roles during malignant transformation, invasion and metastasis, the SIBLINGs are proteins with potential as diagnostic and prognostic tools, as well as new therapeutic targets.

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“…Although originally thought to be exclusively expressed by dentin, DSPP is also expressed in bone, cementum and in non-mineralising tissues including the lung and kidney (Qin et al 2002, Baba et al 2004, Alvares et al 2006, Ogbureke & Fisher 2007, Verdelis et al 2008.…”

Section: Dentin Sialophosphoproteinmentioning

confidence: 99%

The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling

Staines¹,

MacRae²,

Farquharson³

2012

Journal of Endocrinology

189

109

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The small integrin-binding ligand N-linked glycoprotein (SIBLING) family consists of osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. These proteins share many structural characteristics and are primarily located in bone and dentin. Accumulating evidence has implicated the SIBLING proteins in matrix mineralisation. Therefore, in this review, we discuss the individual role that each of the SIBLING proteins has in this highly orchestrated process. In particular, we emphasise how the nature and extent of their proteolytic processing and post-translational modification affect their functional role. Finally, we describe the likely roles of the SIBLING proteins in clinical disorders of hypophosphataemia and their potential therapeutic use.

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SIBLING Expression Patterns in Duct Epithelia Reflect the Degree of Metabolic Activity

Cited by 79 publications

References 44 publications

Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells

Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells

Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer

The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling

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