文章：

小整合素结合配体n-连接糖蛋白：癌症中的多功能蛋白

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

原文发布日期：2008-03-01

DOI: 10.1038/nrc2345

类型: Review Article

开放获取: 否

要点：

1. Small integrin-binding ligand N-linked glycoproteins (SIBLINGs) are a family of glycophosphoproteins comprising osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE).
2. The genes encoding the SIBLINGs are located within a cluster on chromosome 4 and encode soluble, hydrophilic proteins sharing common functional motifs and domains, including an Arg–Gly–Asp (RGD) motif that binds αvβ3 integrin.
3. SIBLINGs were initially described as mineralized tissue-associated glycophosphoproteins and were thought to be functionally restricted to these tissues. Recent results show that they are more widely distributed and are expressed in non-mineralized normal tissue, such as metabolically active ductal epithelial cells.
4. Some SIBLINGs activate specific metalloproteinases (MMPs; BSP activates MMP2, OPN, MMP3 and DMP1, MMP9). These three SIBLINGs also bind complement factor H and prevent complement attack.
5. SIBLINGs are overexpressed in many cancers. OPN and, less so, BSP are by far the more widely studied to date and their levels of expression are correlated with tumour aggressiveness. SIBLINGs can be detected in the blood and their level of expression is associated with prognosis.
6. Among SIBLINGs, OPN is involved in almost all steps of tumour progression, including invasion, metastasis and angiogenesis.
7. In vitro and in vivo experimental models demonstrated that interference with SIBLINGs, such as small interfering RNA selective knockdown, has potential anticancer therapeutic value.
8. Identifying the specific roles of SIBLINGs in cancer–stroma interactions and signalling cascades involving growth factor–growth factor receptor and cell–matrix interactions could result in the development of additional and refined strategies for the prevention and treatment of metastases.

要点翻译：

1. 小整合素结合配体N-连接糖蛋白（SIBLINGs）是一个糖磷蛋白家族，包括骨桥蛋白（OPN）、骨唾液蛋白（BSP）、牙本质基质蛋白1（DMP1）、牙本质唾液磷蛋白（DSPP）和基质细胞外磷糖蛋白（MEPE）。
2. 编码SIBLINGs的基因位于4号染色体上的一个基因簇内，编码可溶性亲水蛋白，这些蛋白共享常见功能基序和结构域，包括结合αvβ3整合素的精氨酸-甘氨酸-天冬氨酸（RGD）基序。
3. SIBLINGs最初被描述为与矿化组织相关的糖磷蛋白，并被认为功能上仅限于这些组织。最近的研究结果表明，它们分布更广，在非矿化的正常组织（如代谢活跃的导管上皮细胞）中也有表达。
4. 部分SIBLINGs能激活特定金属蛋白酶（BSP激活MMP2，OPN激活MMP3，DMP1激活MMP9）。这三种SIBLINGs还能结合补体因子H并阻止补体攻击。
5. SIBLINGs在多种癌症中过度表达。迄今为止，OPN及程度稍弱的BSP是研究最为广泛的成员，其表达水平与肿瘤侵袭性相关。SIBLINGs可在血液中检测到，其表达水平与预后相关。
6. 在SIBLINGs家族中，OPN参与肿瘤进展的几乎所有步骤，包括侵袭、转移和血管生成。
7. 体外和体内实验模型证实，通过小干扰RNA选择性敲除等方式干扰SIBLINGs具有潜在抗癌治疗价值。
8. 明确SIBLINGs在癌症-间质相互作用、生长因子-生长因子受体信号级联及细胞-基质相互作用中的具体角色，或可为预防和治疗转移瘤制定更完善的新策略。

英文摘要：

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.

摘要翻译： 

癌细胞与其微环境之间复杂的相互作用涉及众多组分和信号通路。糖磷蛋白家族成员——包括骨桥蛋白、骨唾液酸蛋白、牙本质基质蛋白1、牙本质唾液酸磷蛋白及基质细胞外磷酸糖蛋白——统称为小整合素结合配体N-连接糖蛋白（SIBLINGs），正日益被视为癌症进展多个阶段的重要参与者。从在多种人类肿瘤中被检测到，到其在恶性转化、侵袭和转移等关键过程中发挥的功能作用，SIBLINGs不仅具备成为诊断和预后工具的潜力，也有望成为新的治疗靶点。

原文链接：

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