Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA; Eppley Institute for Research in Cancer and Allied Diseases, USA; Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
Biochim Biophys Acta Rev Cancer. 2024 Jan;1879(1):189029. doi: 10.1016/j.bbcan.2023.189029. Epub 2023 Nov 24.
Asporin (ASPN) has been identified as one of the members of the class I small leucine-rich proteoglycans (SLRPs) family in the extracellular matrix (ECM). It is involved in classic ensigns of cancers such as self-dependent growth, resistance to growth inhibitors, restricting apoptosis, cancer metastasis, and bone-related disorders. ASPN is different from other members of SLRPs, such as decorin (DCN) and biglycan (BGN), in a way that it contains a distinctive length of aspartate (D) residues in the amino (N) -terminal region. These D-repeats residues possess germline polymorphisms and are identified to be linked with cancer progression and osteoarthritis (OA). The polyaspartate stretch in the N-terminal region of the protein and its resemblance to DCN are the reasons it is called asporin. In this review, we comprehensively summarized and updated the dual role of ASPN in various malignancies, its structure in mice and humans, variants, mutations, cancer-associated signalings and functions, the relationship between ASPN and cancer-epithelial, stromal fibroblast crosstalk, immune cells and immunosuppression in cancer and other diseases. In cancer and other bone-related diseases, ASPN is identified to be regulating various signaling pathways such as TGFβ, Wnt/β-catenin, notch, hedgehog, EGFR, HER2, and CD44-mediated Rac1. These pathways promote cancer cell invasion, proliferation, and migration by mediating the epithelial-to-mesenchymal transition (EMT) process. Finally, we discussed mouse models mimicking ASPN in vivo function in cancers and the probability of therapeutic targeting of ASPN in cancer cells, fibrosis, and other bone-related diseases.
天冬酰胺聚糖（ASPN）已被鉴定为细胞外基质（ECM）中 I 类小富含亮氨酸的蛋白聚糖（SLRPs）家族的成员之一。它参与了癌症的经典标志，如自主生长、抵抗生长抑制剂、限制细胞凋亡、癌症转移和与骨骼相关的疾病。ASPN 与 SLRPs 的其他成员（如饰胶蛋白（DCN）和 BIGLYCAN（BGN））不同，它在氨基（N）-末端区域含有独特长度的天冬氨酸（D）残基。这些 D-重复残基具有种系多态性，被认为与癌症进展和骨关节炎（OA）有关。该蛋白 N 端的多聚天冬氨酸链及其与 DCN 的相似性是其被称为天冬酰胺聚糖的原因。在这篇综述中，我们全面总结和更新了 ASPN 在各种恶性肿瘤中的双重作用、它在小鼠和人类中的结构、变体、突变、与癌症相关的信号和功能、ASPN 与癌症上皮细胞、基质成纤维细胞的相互作用以及在癌症和其他疾病中的免疫细胞和免疫抑制作用。在癌症和其他与骨骼相关的疾病中，ASPN 被鉴定为调节 TGFβ、Wnt/β-catenin、Notch、Hedgehog、EGFR、HER2 和 CD44 介导的 Rac1 等各种信号通路。这些途径通过介导上皮-间充质转化（EMT）过程促进癌细胞的侵袭、增殖和迁移。最后，我们讨论了模拟 ASPN 在体内癌症功能的小鼠模型以及在癌症细胞、纤维化和其他骨骼相关疾病中靶向治疗 ASPN 的可能性。
